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Mechanism of stilbene glycosides on apoptosis of SH-SY5Y cells via regulating PI3K/AKT signaling pathway
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作者 KANG Bi-qian LI Yue +8 位作者 HE Xiao-xuan XIAO Zhen HU Rui LUO Chen-liang QIAO Ming-yu WU Gui-you LI Zhen-zhong ZHU Xiao-ying HUANG Zhong-shi 《Journal of Hainan Medical University》 CAS 2024年第1期8-14,共7页
Objective:To investigate the effects of stilbene glycoside(TSG)on okadaic acid-induced apoptosis in human neuroblastoma cells(SH-SY5Y)via the PI3K/AKT pathway.Methods:The optimal concentration of OA was screened by CC... Objective:To investigate the effects of stilbene glycoside(TSG)on okadaic acid-induced apoptosis in human neuroblastoma cells(SH-SY5Y)via the PI3K/AKT pathway.Methods:The optimal concentration of OA was screened by CCK-8 assay,and SH-SY5Y cells were divided into control group,model group,TSG group,LY294002 group and LY294002+TSG group.The proliferation and apoptosis in each group were detected by CCK-8 and TUNEL assays;Western blotting method and real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of PI3K,P-PI3K(Y607),AKT,P-AKT(Ser473),Bcl-2 and Bax proteins.The relative protein expression was represented by P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT and Bcl-2/Bax gray ratio.Results:CCK-8 screened the optimal concentration of OA as 40 nmol/L.Compared with the control group,the model group increased relative cell viability,decreased apoptosis rate,the pathway and apoptotic proteins expression levels of P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT and Bcl-2/Bax were decreased,and the mRNA expression levels of PI3K,AKT and Bcl-2 were decreased.Bax mRNA expression level increased(P<0.05);Compared with model group,TSG group increased relative cell viability,decreased apoptosis rate,increased protein expression levels of P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT,Bcl-2/Bax,and increased mRNA expression levels of PI3K,AKT,and Bcl-2.Bax mRNA expression decreased(P<0.05),LY294002 group decreased relative cell viability,increased apoptosis rate,P-PI3K(Y607)/PI3K protein expression levels were significantly decreased(P<0.05),P-AKT(Ser473)/AKT and Bcl-2/Bax protein expression levels were significantly decreased,but there was no statistical significance,PI3K,AKT and Bcl-2 mRNA expression levels were decreased,and Bax mRNA expression levels were increased(all P<0.05);Compared with LY294002 group,LY294002+TSG group increased relative cell viability,decreased apoptosis rate,and the protein expression levels of P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT and Bcl-2/Bax were increased.The mRNA expression levels of PI3K,AKT,Bcl-2 were increased,Bax was decreased(all P<0.05).Conclusion:Stilbene glycoside may alleviate okadaic acid-induced apoptosis in SH-SY5Y cells by interfering with the PI3K/AKT signaling pathway,which in turn regulates the expression of apoptotic factors such as Bcl-2 and Bax. 展开更多
关键词 2 3 5 4'-tetrahydroxystilbene 2-O-glucopyranoside Alzheimer disease LY294002 Phosphatidylinositol 3-kinase(pi3k)/protein kinase b(akt) Cell proliferation APOPTOSIS
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乌丹丸对寒凝血瘀子宫内膜异位大鼠PI3K/Akt/mTOR自噬信号轴及相关分子表达的影响 被引量:5
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作者 张家蔚 薛晓鸥 +5 位作者 严培嘉 祝洁 李军 贺稚平 代勇 孙海芸 《环球中医药》 CAS 2023年第2期183-190,共8页
目的探讨乌丹丸对寒凝血瘀型子宫内膜异位症(endometriosis,EMs)大鼠自噬信号轴磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,PKB又称Akt)/雷帕霉素靶分子(mammalian target of rapamycin,mTOR)... 目的探讨乌丹丸对寒凝血瘀型子宫内膜异位症(endometriosis,EMs)大鼠自噬信号轴磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,PKB又称Akt)/雷帕霉素靶分子(mammalian target of rapamycin,mTOR)及相关分子表达的影响。方法随机将49只雌性SD大鼠分为假手术组、模型组、乌丹丸高、中、低剂量组、散结镇痛胶囊组、地诺孕素组,每组7只,采用冰水浴联合自体子宫内膜移植法建立寒凝血瘀EMs大鼠模型。假手术组及模型组每天给予10 mL/kg生理盐水灌胃,乌丹丸高、中、低剂量组分别给予2.4 g/kg、1.2 g/kg、0.6 g/kg灌胃,散结镇痛胶囊组每天给予0.48 g/kg灌胃,地诺孕素组每天给予0.2 mg/kg灌胃,各组持续用药28日。应用蛋白免疫印迹法和免疫组化法检测异位内膜组织自噬信号轴PI3K、p-Akt、p-mTOR蛋白以及相关自噬分子LC3、Beclin-1蛋白表达。结果与假手术组比较,模型组大鼠异位内膜组织PI3K/Akt/mTOR蛋白表达上调,Beclin-1、LC3蛋白表达下调(P<0.01)。中药干预后,乌丹丸高、中剂量组、散结镇痛胶囊组和地诺孕素组异位内膜上PI3K/Akt/mTOR蛋白表达降低,而Beclin-1、LC3蛋白表达升高,与模型组比较差异有统计学意义(P<0.01,P<0.05)。结论PI3K/Akt/mTOR信号通路参与子宫内膜异位症发生,乌丹丸可能通过下调PI3K/Akt/mTOR通路蛋白的表达,激活自噬相关蛋白LC3、Beclin-1表达,促进细胞自噬,治疗子宫内膜异位症。 展开更多
关键词 乌丹丸 子宫内膜异位症 磷脂酰肌醇-3-激酶/蛋白激酶b/雷帕霉素靶分子(pi3k/akt/mTOR)信号通路 自噬 寒凝血瘀
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红景天苷通过激活PI3K/AKT通路抑制氧化应激和免疫炎症反应减轻糖尿病大鼠视网膜病变 被引量:4
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作者 张佑靖 杨明 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2023年第5期404-409,共6页
目的探讨红景天苷对糖尿病大鼠视网膜病变(DR)的改善作用及其机制。方法雄性SD大鼠随机分为空白组、模型组以及低剂量、高剂量红景天苷处理组;除空白组外,采用腹腔注射链脲佐菌素建立DR大鼠模型,成功后处理组分别腹腔注射[50 mg/(kg... 目的探讨红景天苷对糖尿病大鼠视网膜病变(DR)的改善作用及其机制。方法雄性SD大鼠随机分为空白组、模型组以及低剂量、高剂量红景天苷处理组;除空白组外,采用腹腔注射链脲佐菌素建立DR大鼠模型,成功后处理组分别腹腔注射[50 mg/(kg·d)]和[100 mg/(kg·d)]红景天苷,连续4周;空白组和模型组则注射相应剂量的生理盐水。采用ELISA检测各组大鼠血糖及血清中抗氧化相关酶活力及炎症因子表达水平;采用HE染色法检测视网膜组织病变,并采用免疫组织化学染色法检测视网膜组织中血管内皮生长因子(VEGF)和细胞间黏附分子1(ICAM⁃1)的表达情况,用Western blot法检测磷脂酰肌醇3激酶(PI3K)、核因子κB p65(NF⁃κB p65)、磷酸化p38 MAPK(p⁃p38 MAPK)、磷酸化蛋白激酶B(p⁃AKT)蛋白表达。结果红景天苷能显著降低DR大鼠血糖水平、增加体质量,显著提高模型大鼠血清超氧化物歧化酶(SOD)和过氧化氢酶(CAT)水平,降低丙二醛(MDA)、肿瘤坏死因子α(TNF⁃α)、白细胞介素6(IL⁃6)和IL⁃1β水平;并能够显著性降低VEGF、ICAM⁃1、NF⁃κB p65和p⁃p38 MAPK蛋白表达,增加PI3K和p⁃AKT蛋白表达。结论红景天苷通过抑制机体氧化应激和免疫炎症反应减轻大鼠DR,可能与降低VEGF和ICAM⁃1的异常表达以及激活PI3K/AKT信号通路有关。 展开更多
关键词 糖尿病视网膜病变(DR) 红景天苷 磷脂酰肌醇3激酶(pi3k) 蛋白激酶b(akt) 免疫炎症反应
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PI3K/Akt pathway is involved in the activation of RAW 264.7 cells induced by hydroxypropyltrimethyl ammonium chloride chitosan
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作者 YANG Yue XING Rong’e +4 位作者 LIU Song QIN Yukun LI Kecheng YU Huahua LI Pengcheng 《Journal of Oceanology and Limnology》 SCIE CAS CSCD 2020年第3期834-840,共7页
We previously demonstrated that 2-hydroxypropyltrimethyl ammonium chloride chitosan(HACC)promoted the production of nitric oxide(NO)and proinflammatory cytokines by activating the mitogen-activated protein kinases(MAP... We previously demonstrated that 2-hydroxypropyltrimethyl ammonium chloride chitosan(HACC)promoted the production of nitric oxide(NO)and proinflammatory cytokines by activating the mitogen-activated protein kinases(MAPK)and Janus kinase(JAK)/STAT pathways in RAW 264.7 cells,indicating good immunomodulatory activity of HACC.In this study,to further investigate the immunomodulatory mechanisms of HACC,we determined the roles of phosphatidylinositol 3-kinase(PI3K)/Akt,activating protein(AP-1)and nuclear factor kappa B(NF-κB)in HACC-induced activation of RAW 264.7 cells by the western blotting.The results suggest that HACC promoted the phosphorylation of p85 and Akt.Furthermore,c-Jun and p65 were also increased after the treatment of RAW 264.7 cells with HACC,indicating the translocation of NF-κB and AP-1 from cytoplasm to nucleus.In addition,as scanning electron microscopy(SEM)analysis shows,the cell morphology changed after HACC treatment.These findings indicate that HACC activated MAPK,JAK/STAT,and PI3K/Akt signaling pathways dependent on AP-1 and NF-κB activation in RAW 264.7 cells,ultimately leading to the increase of NO and cytokines. 展开更多
关键词 hydroxypropyltrimethyl AMMONIUM chloride CHITOSAN RAW 264.7 CELLS pi3k/akt pathway nuclear factor-κb ACTIVATING protein 1
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Regulatory Effects of Zuogui Pill on Apoptosis of Follicles in Rats Injured by 60Co-γRays Based on PI3K/Akt/m TOR Signaling Pathway
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作者 Fenqin ZHAO Mingxia AN +4 位作者 Xiaonan DING Jieying LIU Yan ZHAO Zhihui XIE Shuping LI 《Medicinal Plant》 CAS 2022年第5期45-50,58,共7页
[Objectives]To explore the protective effects of Zuogui Pill on ^(60)Co-γ-ray-induced premature aging of rats based on phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signal... [Objectives]To explore the protective effects of Zuogui Pill on ^(60)Co-γ-ray-induced premature aging of rats based on phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway.[Methods]Sixty sexually mature female SD rats were irradiated with ^(60)Co-γ-ray(6.0 Gy,LD 40)for 24 h at one time.These rats were randomly divided into model group,Progynova group[0.18(g·kg)/d],Progynova[0.09(g·kg)/d]+Zuogui Pill high dose[23.625(g·kg)/d)]group,Zuogui Pill high dose[23.625(g·kg)/d)]group,Zuogui Pill medium dose[9.45(g·kg)/d)]group and Zuogui Pill low dose[4.725(g·kg)/d]group.The administration(once a day)lasted 21 d.The rat serum[follicle-stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E_(2))]were detected by Enzyme-linked immunosorbent assay(ELISA).The morphological changes of ovary were observed by hematoxylin-eosin(HE)staining.The apoptosis rate of granulosa cells was detected by terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL).The protein expression of phosphorylated(p)-PI3K,p-Akt,p-mTOR,B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in ovarian tissues were detected by Western blot.[Results]Compared with the normal group,the model group showed significant increase in the serum FSH(P<0.01),significant decrease in serum E_(2)(P<0.05),and decrease in the number of early follicles and luteum in the ovary(P<0.01).Besides,the apoptosis rate of granulosa cells increased significantly(P<0.01);the expression of p-PI3K,p-Akt,p-mTOR and Bcl-2 in ovarian tissue decreased significantly,while the expression of Bax increased significantly(P<0.01).Compared with the model group,the number of early follicles in the ovary increased and the apoptosis rate of granulosa cells decreased after intervention in each administration group.In addition,the protein expressions of p-PI3K,p-Akt,p-mTOR and Bcl-2 increased,while the expression of Bax decreased,especially in Progynova+Zuogui Pill high dose group,the differences were statistically significant(P<0.05,P<0.01).[Conclusions]Zuogui Pill may protect the radiation-injured ovary through activating the expression of PI3K/Akt/mTOR protein in ovarian tissue,increasing the amount of Bcl-2 protein and inhibiting the expression of Bax protein. 展开更多
关键词 Radiation injury Premature ovarian failure(POF) Zuogui pill Terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL) Phosphatidylinositol-3-kinases/protein kinase b/mammalian target of rapamycin(pi3k/akt/mTOR)signaling pathway b-cell lymphoma-2 bcl-2-associated X protein
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PI3K/Akt/mTOR inhibitors in breast cancer 被引量:22
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作者 Joycelyn JX Lee Kiley Loh Yoon-Sim Yap 《Cancer Biology & Medicine》 SCIE CAS CSCD 2015年第4期342-354,共13页
Activation of the phosphoinositide 3 kinase(PI3K)/Akt/mammalian target of rapamycin(mTOR) pathway is common in breast cancer. There is preclinical data to support inhibition of the pathway, and phase Ⅰ to Ⅲ trials i... Activation of the phosphoinositide 3 kinase(PI3K)/Akt/mammalian target of rapamycin(mTOR) pathway is common in breast cancer. There is preclinical data to support inhibition of the pathway, and phase Ⅰ to Ⅲ trials involving inhibitors of the pathway have been or are being conducted in solid tumors and breast cancer. Everolimus, an mTOR inhibitor, is currently approved for the treatment of hormone receptor(HR)-positive, human epidermal growth factor receptor 2(HER2)-negative breast cancer. In this review, we summarise the efficacy and toxicity findings from the randomised clinical trials, with simplified guidelines on the management of potential adverse effects. Education of healthcare professionals and patients is critical for safety and compliance. While there is some clinical evidence of activity of mTOR inhibition in HR-positive and HER2-positive breast cancers, the benefits may be more pronounced in selected subsets rather than in the overall population. Further development of predictive biomarkers will be useful in the selection of patients who will benefit from inhibition of the PI3K/Akt/mTOR(PAM) pathway. 展开更多
关键词 breast cancer phosphoinositide 3 kinase(pi3k/akt/ mammalian target of rapamycin(mTOR) everolimus
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Insensitivity of PI3K/Akt/GSK3 signaling in peripheral blood mononuclear cells of age-related macular degeneration patients 被引量:2
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作者 Xunxian Liu Zemin Yao 《The Journal of Biomedical Research》 CAS CSCD 2017年第3期248-255,共8页
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C(IL-17RC),a phenomenon observed in peripheral blood and chorioretinal tissues with age-rela... Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C(IL-17RC),a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration(AMD),was associated with altered activation of phosphatidylinositide 3-kinase(PI3K),Akt,and glycogen synthase kinase 3(GSK3).We wondered whether or not altered PI3 K,Akt,and GSK3 activities could be detected in peripheral blood mononuclear cells(PBMC) obtained from AMD patients.In the patients' PBMC,absent or reduced serine-phosphorylation of GSK3α or GSK3β was observed,which was accompanied with increased phosphorylation of GSK3 substrates(e.g.CCAAT enhancer binding protein a,insulin receptor substrate 1,and TAU),indicative of enhanced GSK3 activation.In addition,decreased protein mass of PI3K85α and tyrosinephosphorylation of PI3K50α was present in PBMC of the AMD patients,suggesting impaired PI3 K activation.Moreover,abnormally lowered molecular weight forms of Akt and GSK3 were detected in PBMC of the AMD patients.These data demonstrate that despite the presence of high levels of IL-17 RC,Wnt-3a and vascular endothelial growth factor,the PI3K/Akt/GSK3 signaling pathway is insensitive to these stimuli in PBMC of the AMD patients.Thus,measurement of PI3K/Akt/GSK3 expression and activity in PBMC may serve as a surrogate biomarker for AMD. 展开更多
关键词 phosphatidylinositide 3-kinase (pi3k protein kinase b (Pkb or akt) glycogen synthase kinase 3(GSk3 age-related macular degeneration (AMD) peripheral blood mononuclear cells (PbMC)
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Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice 被引量:1
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作者 WEI Ya-ru HOU Yun-long +10 位作者 YIN Yu-jie LI Zhen LIU Yi HAN Ning-xin WANG Zi-xuan LIU Lu WANG Xiao-qi HAO Yuan-jie MA Kun GU Jiao-jiao JIA Zhen-hua 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2024年第7期608-615,共8页
Objective To investigate the potential role of Tongxinluo(TXL)in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI)in mice.Methods A MIRI mouse model was established by left anterior de... Objective To investigate the potential role of Tongxinluo(TXL)in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI)in mice.Methods A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min.According to a random number table,66 mice were randomly divided into 6 groups(n=11 per group):the sham group,the model group,the LY-294002 group,the TXL group,the TXL+LY-294002 group and the benazepril(BNPL)group.The day after modeling,TXL and BNPL were administered by gavage.Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks.Echocardiography was used to measure cardiac function in mice.Masson staining was used to evaluate the degree of myocardial fibrosis in mice.Qualitative and quantitative analysis of endothelial mesenchymal transition(EndMT)after MIRI was performed by immunohistochemistry,immunofluorescence staining and flow cytometry,respectively.The protein expressions of platelet endothelial cell adhesion molecule-1(CD31),α-smoth muscle actin(α-SMA),phosphatidylinositol-3-kinase(PI3K)and phospho protein kinase B(p-AKT)were assessed using Western blot.Results TXL improved cardiac function in MIRI mice,reduced the degree of myocardial fibrosis,increased the expression of CD31 and inhibited the expression ofα-SMA,thus inhibited the occurrence of EndMT(P<0.05 or P<0.01).TXL significantly increased the protein expressions of PI3K and p-AKT(P<0.05 or P<0.01).There was no significant difference between TXL and BNPL group(P>0.05).In addition,the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention,eliminated the protective effect of TXL,further supporting the protective effect of TXL.Conclusion TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice. 展开更多
关键词 myocardial fibrosis endothelial mesenchymal transition myocardial ischemia-reperfusion injury phosphatidylinositol-3-kinase/protein kinase b(pi3k/akt)pathway
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PI3K/AKT信号通路与辐射抵抗机制的研究概况
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作者 秦俭 陆合明 陈甲信 《中国临床新医学》 2015年第8期799-802,共4页
辐射抵抗的三个主要机制为内在辐射敏感性、肿瘤细胞增殖和乏氧。磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)信号通路是肿瘤细胞的存活通路之一,该通路的激活与辐射抵抗密切相关。该文就PI3K/AKT信号通路与辐射抵抗机制作一综述。
关键词 放射治疗 磷脂酰肌醇3激酶 蛋白激酶b 辐射抵抗
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PI3K/Akt通路在肝癌细胞迁移和侵袭中的作用 被引量:17
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作者 曹煜姗 孙达权 +2 位作者 夏庆 彭明兵 徐国强 《山东医药》 CAS 2018年第26期14-17,共4页
目的探讨PI3K/Akt信号通路中3-磷酸肌醇-依赖性激酶1(PDK1)、10号染色体上的磷酸酶和张力蛋白同源蛋白(PTEN)、蛋白激酶B(Akt)表达对肝癌细胞迁移和侵袭的作用。方法常规培养肝癌SMMC-7721细胞,将细胞分为对照组、PDK1抑制剂组、Akt激... 目的探讨PI3K/Akt信号通路中3-磷酸肌醇-依赖性激酶1(PDK1)、10号染色体上的磷酸酶和张力蛋白同源蛋白(PTEN)、蛋白激酶B(Akt)表达对肝癌细胞迁移和侵袭的作用。方法常规培养肝癌SMMC-7721细胞,将细胞分为对照组、PDK1抑制剂组、Akt激动剂组、PTEN抑制剂组。对照组加入RPMI-1640培养基,PDK1抑制剂组加入PDK1的特异性抑制剂OSU03012,Akt激动剂组加入Akt特异性激动剂SC79,PTEN抑制剂组加入PTEN特异性抑制剂VO-Ohpic。采用细胞划痕实验检测各组细胞迁移能力,Transwell小室检测细胞侵袭能力,Western blotting法检测PDK1基因相关蛋白PDK1、p-PDK1、E-钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)及PTEN、Akt蛋白表达。结果与对照组比较,PDK1抑制剂组细胞迁移率减少,Akt激动剂组和PTEN抑制剂组细胞迁移率增加(P<0.05或<0.01)。与对照组比较,PDK1抑制剂组穿膜细胞数减少,Akt激动剂组和PTEN抑制剂组穿膜细胞数增加(P均<0.01)。与对照组比较,PDK1抑制剂组PDK1、p-PDK1表达降低,E-cadherin表达升高,Vimentin表达降低;Akt激动剂组Akt表达升高,PTEN表达降低;PTEN抑制剂组PTEN表达降低,Akt表达升高(P<0.05或<0.01)。结论抑制PI3K/Akt信号通路中PDK1表达可以抑制肝癌细胞迁移和侵袭,促进Akt和抑制PTEN表达可以促进肝癌细胞迁移和侵袭。 展开更多
关键词 肝细胞癌 pi3k/akt信号通路 3-磷酸肌醇-依赖性激酶1 10号染色体上的磷酸酶和张力蛋白同源蛋白 蛋白激酶b 细胞迁移 细胞侵袭
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Scorpiones,Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1αSignaling Pathway
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作者 MAO Qi-yuan WANG Xue-qian +7 位作者 LIN Fei YU Ming-wei FAN Hui-ting ZHENG Qi LIU Lan-chun ZHANG Chu-chu LI Dao-rui LIN Hong-sheng 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2024年第9期799-808,共10页
Objective:To investigate whether Buthus martensii karsch(Scorpiones),Scolopendra subspinipes mutilans L.Koch(Scolopendra)and Gekko gecko Linnaeus(Gekko)could ameliorate the hypoxic tumor microenvironment and inhibit l... Objective:To investigate whether Buthus martensii karsch(Scorpiones),Scolopendra subspinipes mutilans L.Koch(Scolopendra)and Gekko gecko Linnaeus(Gekko)could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α(PI3K/AKT/mTOR/HIF-1α)signaling pathway.Methods:Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models,with rapamycin and cyclophosphamide as positive controls.Carboxy methyl cellulose solutions of Scorpiones,Scolopendra and Gekko were administered intragastrically as 0.33,0.33,and 0.83 g/kg,respectively once daily for 21 days.Fluorescent expression were detected every 7 days after inoculation,and tumor growth curves were plotted.Immunohistochemistry was performed to determine CD31 and HIF-1αexpressions in tumor tissue and microvessel density(MVD)was analyzed.Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1αsignaling pathway-related proteins.Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor(bFGF),transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF)in mice.Results:Scorpiones,Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α(all P<0.01).Moreover,Scorpiones,Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase(p70S6K)(P<0.05 or P<0.01).In addition,they also decreased the expression of CD31,MVD,bFGF,TGF-β1 and VEGF compared with the model group(P<0.05 or P<0.01).Conclusion:Scorpiones,Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1αsignaling pathway. 展开更多
关键词 SCORpiONES SCOLOPENDRA Gekko dredging collaterals and activating blood Chinese medicine of worms lung cancer hypoxic tumor microenvironment phosphoinositide 3-kinase/protein kinase b/mammalian target of rapamycin/hypoxia-inducible factor-1α signaling pathway
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紫草素通过调节PI3K/AKT途径抑制骨肉瘤生长和作用机制研究 被引量:9
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作者 杨志强 陈路 +1 位作者 张雅茜 夏先学 《中国比较医学杂志》 CAS 北大核心 2022年第1期68-74,96,共8页
目的研究紫草素(shikonin,SK)的抗骨肉瘤作用及其机制。方法不同浓度的SK处理人骨肉瘤U2OS和MG63细胞及人成骨细胞HFOB1.1924 h或用SK 1μmol/L分别处理24、48和72 h后,CCK-8检测细胞活性;SK 0、0.01、0.1、1μmol/L处理U2OS细胞,克隆... 目的研究紫草素(shikonin,SK)的抗骨肉瘤作用及其机制。方法不同浓度的SK处理人骨肉瘤U2OS和MG63细胞及人成骨细胞HFOB1.1924 h或用SK 1μmol/L分别处理24、48和72 h后,CCK-8检测细胞活性;SK 0、0.01、0.1、1μmol/L处理U2OS细胞,克隆形成实验检测细胞增殖;流式检测细胞凋亡,Western blot检测凋亡相关蛋白的表达;U2OS细胞分为对照组,SK1μmol/L组,PI3K激活剂胰岛素样生长因子1(IGF-1)组和SK1μmol/L+IGF-1组,Western blot检测磷脂酰肌醇3-激酶(PI3K)和蛋白激酶B(AKT)磷酸化、胱天蛋白酶(caspase-3,cas3)、cleaved cas3、Ki67及干细胞标记物SOX-2、OCT-4和Nanog的表达;细胞成球实验检测细胞成球能力。右侧腹皮下注射U2OS细胞构建移植瘤裸鼠模型并进行体内验证。结果不同浓度的SK对HFOB1.19细胞无明显毒性作用,而对U2OS和MG63细胞有显著毒性作用(P<0.05),且具有浓度和时间依赖性。紫草素0.1和1μmol/L可显著抑制U2OS细胞增殖和干细胞样特征,诱导细胞凋亡(P<0.05),并抑制PI3K和AKT蛋白的磷酸化(P<0.05)。IGF-1明显逆转紫草素对PI3K/AKT信号通路的抑制作用,以及对U2OS细胞增殖、凋亡,干细胞样特征的影响(P<0.05)。体内实验表明,紫草素能显著抑制肿瘤的生长(P<0.05),并下调瘤组织中p-AKT的表达(P<0.05)。结论紫草素对骨肉瘤U2OS细胞生长和干细胞样特征的抑制作用可能与抑制PI3K/AKT信号通路的激活有关。 展开更多
关键词 骨肉瘤 紫草素 增殖 细胞凋亡 干细胞样特征 磷酸肌醇3-激酶/蛋白激酶b
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养心定悸胶囊治疗帕金森病合并抑郁患者的临床疗效及对PI3K、AKT、mTOR蛋白水平的影响 被引量:4
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作者 韩雪娟 孔祥芳 戴京涛 《世界中西医结合杂志》 2022年第7期1346-1350,共5页
目的基于磷脂酰肌醇-3-激酶/蛋白激酶B/雷帕霉素靶体蛋白(PI3K/AKT/mTOR)信号通路探讨养心定悸胶囊对帕金森病(Parkinson′s disease,PD)合并抑郁患者的疗效。方法选取2018年1月—2021年1月期间河北中医学院第二附属医院收治的PD合并抑... 目的基于磷脂酰肌醇-3-激酶/蛋白激酶B/雷帕霉素靶体蛋白(PI3K/AKT/mTOR)信号通路探讨养心定悸胶囊对帕金森病(Parkinson′s disease,PD)合并抑郁患者的疗效。方法选取2018年1月—2021年1月期间河北中医学院第二附属医院收治的PD合并抑郁患者102例,随机分为对照组和研究组,每组各51例。对照组接受常规西药治疗,研究组在对照组基础上加用养心定悸胶囊。治疗12周后,观察比较两组患者临床疗效,治疗前后统一帕金森病评分量表(Unified Parkinson′s Disease Rating Scale,UPDRS)评分、帕金森病自主神经症状量表(SPOCA-AUT)评分、汉密尔顿抑郁量表(Hamilton depression scale,HAMD)评分及血清PI3K、AKT、mTOR蛋白水平情况。结果治疗后研究组总有效率92.16%(47/51)较对照组76.47%(39/51)明显升高,差异有统计学意义(P<0.05)。治疗后两组患者各项UPDRS评分及总分均低于治疗前,差异有统计学意义(P<0.05);且研究组各项UPDRS评分及总分低于对照组,差异有统计学意义(P<0.05)。治疗后研究组消化、心血管系统、体温调节、瞳孔调节评分及SCOPA-AUT总分均低于治疗前,差异有统计学意义(P<0.05);且研究组消化、心血管系统、体温调节、瞳孔调节评分及SCOPA-AUT总分均低于对照组,差异有统计学意义(P<0.05)。治疗后研究组HAMD评分低于治疗前,差异有统计学意义(P<0.05);且研究组HAMD评分低于对照组,差异有统计学意义(P<0.05)。治疗后研究组PI3K、AKT、mTOR蛋白表达水平均低于对照组,差异均有统计学意义(P<0.05)。结论养心定悸胶囊对PD合并抑郁患者具有较好的疗效,可缓解病情发展,改善非运动症状,并能减轻抑郁情绪,可能是通过影响PI3K/AKT/mTOR信号通路而发挥作用。 展开更多
关键词 帕金森病 抑郁 养心定悸胶囊 磷脂酰肌醇-3-激酶 蛋白激酶b 雷帕霉素靶体蛋白
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Bone marrow-derived mesenchymal stem cells modulate autophagy in RAW264.7 macrophages via the phosphoinositide 3-kinase/protein kinase B/heme oxygenase-1 signaling pathway under oxygen-glucose deprivation/restoration conditions 被引量:6
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作者 Ning-Fang Wang Chun-Xue Bai 《Chinese Medical Journal》 SCIE CAS CSCD 2021年第6期699-707,共9页
Background: Autophagy of alveolar macrophages is a crucial process in ischemia/reperfusion injury-induced acute lung injury (ALI). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent cells with the po... Background: Autophagy of alveolar macrophages is a crucial process in ischemia/reperfusion injury-induced acute lung injury (ALI). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent cells with the potential for repairing injured sites and regulating autophagy. This study was to investigate the influence of BM-MSCs on autophagy of macrophages in the oxygen-glucose deprivation/restoration (OGD/R) microenvironment and to explore the potential mechanism.Methods: We established a co-culture system of macrophages (RAW264.7) with BM-MSCs under OGD/R conditionsin vitro. RAW264.7 cells were transfected with recombinant adenovirus (Ad-mCherry-GFP-LC3B) and autophagic status of RAW264.7 cells was observed under a fluorescence microscope. Autophagy-related proteins light chain 3 (LC3)-I, LC3-II, and p62 in RAW264.7 cells were detected by Western blotting. We used microarray expression analysis to identify the differently expressed genes between OGD/R treated macrophages and macrophages co-culture with BM-MSCs. We investigated the gene heme oxygenase-1 (HO-1), which is downstream of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.Results: The ratio of LC3-II/LC3-I of OGD/R treated RAW264.7 cells was increased (1.27 ± 0.20vs. 0.44 ± 0.08,t = 6.67,P < 0.05), while the expression of p62 was decreased (0.77 ± 0.04vs. 0.95 ± 0.10,t = 2.90,P < 0.05), and PI3K (0.40 ± 0.06vs. 0.63 ± 0.10,t = 3.42,P < 0.05) and p-Akt/Akt ratio was also decreased (0.39 ± 0.02vs. 0.58 ± 0.03,t = 9.13,P < 0.05). BM-MSCs reduced the LC3-II/LC3-I ratio of OGD/R treated RAW264.7 cells (0.68 ± 0.14vs. 1.27 ± 0.20,t = 4.12,P < 0.05), up-regulated p62 expression (1.10 ± 0.20vs. 0.77 ± 0.04,t = 2.80,P < 0.05), and up-regulated PI3K (0.54 ± 0.05vs. 0.40 ± 0.06,t = 3.11,P < 0.05) and p-Akt/Akt ratios (0.52 ± 0.05vs. 0.39 ± 0.02,t = 9.13,P < 0.05). A whole-genome microarray assay screened the differentially expressed geneHO-1, which is downstream of the PI3K/Akt signaling pathway, and the alteration ofHO-1 mRNA and protein expression was consistent with the data on PI3K/Akt pathway.Conclusions: Our results suggest the existence of the PI3K/Akt/HO-1 signaling pathway in RAW264.7 cells under OGD/R circumstancesin vitro, revealing the mechanism underlying BM-MSC-mediated regulation of autophagy and enriching the understanding of potential therapeutic targets for the treatment of ALI. 展开更多
关键词 bone marrow mesenchymal stem cells Oxygen-glucose deprivation/restoration phosphoinositide 3-kinase/protein kinase b signaling pathway Macrophages AUTOPHAGY Whole-genome microarray assay
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PI3K/Akt信号通路与肺纤维化 被引量:17
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作者 刘玲 何振华 《微生物学免疫学进展》 2017年第6期80-84,共5页
肺纤维化(pulmonary fibrosis)是进行性、致命性的疾病。其致病机制不明,治疗效果差。PI3K/Akt信号通路主要与细胞的生长、增殖、分化、凋亡及血管形成等有关。近年来,随着对PI3K/Akt信号通路的深入研究,发现其活化后可激活下游中的一... 肺纤维化(pulmonary fibrosis)是进行性、致命性的疾病。其致病机制不明,治疗效果差。PI3K/Akt信号通路主要与细胞的生长、增殖、分化、凋亡及血管形成等有关。近年来,随着对PI3K/Akt信号通路的深入研究,发现其活化后可激活下游中的一些因子参与肺纤维化,且与其他通路协同作用促进肺纤维化的形成。因此该通路有可能成为治疗肺纤维化的新靶点。将PI3K/Akt信号通路参与肺纤维化形成的研究进展作一综述。 展开更多
关键词 pi3k/akt信号通路 肺纤维化 上下游因子
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黄芪甲苷调节PI3K/AKT/eNOS信号通路对糖尿病大鼠皮肤缺损的影响 被引量:6
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作者 刘东波 李卫 +4 位作者 何藻鹏 郑韬 陈远芬 霍启灿 何欣桥 《中医药导报》 2022年第7期20-26,共7页
目的:探究黄芪甲苷通过调控3-磷酸肌醇激酶(PI3K)/蛋白激酶B(AKT)/内皮型一氧化氮合酶(eNOS)信号通路对糖尿病大鼠皮肤损伤的影响。方法:36只雄性SD大鼠随机分为糖尿病组、皮肤损伤组、护理软膏组、黄芪甲苷高剂量组、黄芪甲苷低剂量组... 目的:探究黄芪甲苷通过调控3-磷酸肌醇激酶(PI3K)/蛋白激酶B(AKT)/内皮型一氧化氮合酶(eNOS)信号通路对糖尿病大鼠皮肤损伤的影响。方法:36只雄性SD大鼠随机分为糖尿病组、皮肤损伤组、护理软膏组、黄芪甲苷高剂量组、黄芪甲苷低剂量组、黄芪甲苷+PI3K抑制剂组,每组6只。除糖尿病组外,其余各组均建立糖尿病大鼠皮肤损伤模型,各给药组分别给予相应干预,糖尿病组和皮肤损伤组不做处理。1次/d,持续用药21 d,记录各时间点(术后7、14、21 d)创面愈合情况;图片记录大鼠术后21 d创面血管生成情况,分析各组大鼠血管化面积比;HE染色和Masson染色观察皮肤病理学变化;检测PI3K/AKT/eNOS信号通路及VEGF/VEGFR信号通路相关基因的mRNA及蛋白的表达情况。结果:术后各时间点大鼠创面愈合率比较,差异有统计学意义(P<0.05),存在时间效应。5组大鼠创面愈合率总体比较,差异有统计学意义(P<0.05),存在分组效应。时间因素与分组因素对大鼠创面愈合率的影响存在交互作用(P<0.05)。与糖尿病组比较,皮肤损伤组大鼠创面组织坏死严重,创面血管化面积比明显降低(P<0.05),PI3K/AKT/eNOS通路相关基因mRNA、蛋白磷酸化表达及VEGF、VEGFR2蛋白表达水平均明显升高(P<0.05);与皮肤损伤组比较,黄芪甲苷高剂量组、黄芪甲苷低剂量组、护理软膏组大鼠创面组织逐渐恢复,创面血管化面积比明显升高(P<0.05),PI3K/AKT/eNOS通路相关基因mRNA、蛋白磷酸化表达及VEGF、VEGFR2蛋白表达水平均明显升高(P<0.05);与黄芪甲苷高剂量组比较,黄芪甲苷低剂量组、黄芪甲苷+PI3K抑制剂组大鼠创面组织恢复缓慢,创面血管化面积比明显降低(P<0.05),PI3K/AKT/eNOS信号蛋白磷酸化水平及VEGF、VEGFR2蛋白表达均明显降低(P<0.05);黄芪甲苷高剂量组各项指标与护理软膏组比较,差异均无统计学意义(P>0.05)。结论:黄芪甲苷可增强糖尿病皮肤缺损模型大鼠PI3K/AKT/eNOS通路激活水平,提高VEGF、VEGFR2蛋白的表达,加速创面组织的恢复和血管生成,缓解皮肤缺损。 展开更多
关键词 糖尿病皮肤损伤 黄芪甲苷 3-磷酸肌醇激酶 蛋白激酶b 内皮型一氧化氮合酶 大鼠
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南非草药蝴蝶亚仙人掌对db/db小鼠肝脏糖脂代谢和PI3K/Akt/FoxO1信号通路的影响
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作者 张程斐 张秋娥 +5 位作者 秦灵灵 刘玮 许光远 马学盛 吴丽丽 刘铜华 《中国实验方剂学杂志》 CAS CSCD 北大核心 2024年第5期57-64,共8页
目的:观察南非草药蝴蝶亚仙人掌(HG)对糖尿病db/db小鼠糖脂代谢的影响,基于磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/叉头转录因子O亚族1(FoxO1)信号通路探索HG对db/db小鼠肝脏可能的机制。方法:30只db/db小鼠根据空腹血糖随机分为5组:模... 目的:观察南非草药蝴蝶亚仙人掌(HG)对糖尿病db/db小鼠糖脂代谢的影响,基于磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/叉头转录因子O亚族1(FoxO1)信号通路探索HG对db/db小鼠肝脏可能的机制。方法:30只db/db小鼠根据空腹血糖随机分为5组:模型组、二甲双胍组(0.195 g·kg^(-1))、HG低剂量组(0.39 g·kg^(-1))、HG中剂量组(0.78 g·kg^(-1))、HG高剂量组(1.56 g·kg^(-1)),每组6只,并设6只m/m小鼠为正常组。正常组和模型组小鼠给予9 mL·kg^(-1)等体积生理盐水灌胃。每周检测各组小鼠体质量、饮食水量及空腹血糖。连续给药6周后取材,测空腹血清胰岛素(FINS)、低密度脂蛋白(LDL)、总胆固醇(TC)、甘油三酯(TG)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、尿素(UREA)、肌酐(CREA),取肝脏包埋切片行苏木素-伊红(HE)、过碘酸雪夫(PAS)及油红O染色。免疫组化检测肝脏中PI3K p85、磷酸化(p)-Akt和p-FoxO1的磷酸化蛋白表达。实时荧光定量聚合酶链式反应(Real-time PCR)检测肝组织中PI3K、Akt、FoxO1 mRNA的表达变化。结果:给药干预6周后发现,与模型组比较,HG低、中、高剂量组小鼠的空腹血糖均明显下调(P<0.05);HG低、中剂量组胰岛抵抗指数水平均有明显降低(P<0.05);HG低、中、高剂量组均可明显降低TC、TG与LDL表达水平(P<0.05,P<0.01);病理方面,与模型组比较,蝴蝶亚仙人掌可缓解小鼠肝细胞脂肪样变性,减轻肝脏内脂滴体积和含量,并一定程度增加肝脏内糖原颗粒的分布。免疫组化检测发现,与模型组比较,HG低、中、高剂量组PI3K p85蛋白表达均显著增加(P<0.01);HG中、高剂量组p-Akt蛋白表达均明显增加(P<0.05,P<0.01);HG低、中、高剂量组p-FoxO1蛋白表达均明显增加(P<0.05,P<0.01)。基因检测发现,与模型组比较,HG低、中、高剂量组PI3K mRNA均明显升高(P<0.05),HG高剂量组Akt mRNA明显升高(P<0.05),HG低、中、高剂量组FoxO1 mRNA均明显降低(P<0.05)。结论:HG可缓解db/db小鼠糖脂代谢紊乱,可能与其激活肝脏PI3K/Akt/FoxO1信号通路有关。 展开更多
关键词 蝴蝶亚仙人掌 糖尿病 db/db小鼠 磷脂酰肌醇3-激酶/蛋白激酶b/叉头转录因子O亚族1(pi3k/akt/FoxO1)信号通路
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Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway
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作者 Jiayi Wang Mengke Zhao +5 位作者 Dong Fu Meina Wang Chao Han Zhongyue Lv Liang Wang Jing Liu 《Neural Regeneration Research》 SCIE CAS 2025年第11期3245-3258,共14页
Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem ce... Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke. 展开更多
关键词 behavior exosome extracellular vesicles ischemic stroke mammalian target of rapamycin(mTOR) middle cerebral artery occlusion neural stem cells neuronal apoptosis phosphoinositide 3-kinase(pi3k) protein kinase b(akt)
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Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis
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作者 Lin Yang Xueying An +7 位作者 Wang Gong Wenshu Wu Bin Liu Xiaoyan Shao Yansi Xian Rui Peng Baosheng Guo Qing Jiang 《Nano Research》 SCIE EI CSCD 2024年第4期2949-2959,共11页
Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of ef... Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy.Here,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption interface.Firstly,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation.Furthermore,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis. 展开更多
关键词 OSTEOPOROSIS Α-CYPERONE OSTEOCLAST phosphoinositide 3-kinase/protein kinase b(pi3k/akt) liposome
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青蒿素基于PI3K/Akt信号通路减轻卵清蛋白哮喘大鼠的气道炎症和气道重塑的分析 被引量:1
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作者 王艳梅 梁彦昌 +1 位作者 甘德堃 赵润杨 《中国实验方剂学杂志》 CAS CSCD 北大核心 2024年第13期114-119,共6页
目的:探究青蒿素通过磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路减轻哮喘气道炎症和气道重塑的分子作用机制。方法:50只雄性SD大鼠随机分为空白组、模型组、青蒿素低、中、高剂量组,每组各10只。建立卵清蛋白(OVA)诱导大鼠哮喘模型... 目的:探究青蒿素通过磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路减轻哮喘气道炎症和气道重塑的分子作用机制。方法:50只雄性SD大鼠随机分为空白组、模型组、青蒿素低、中、高剂量组,每组各10只。建立卵清蛋白(OVA)诱导大鼠哮喘模型,造模成功后,空白组、模型组分别每天给予尾静脉注射1.0 mL·kg^(-1)生理盐水,青蒿素低、中、高剂量组每天给予尾静脉注射青蒿素(12.5、25、50 mg·kg^(-1)),持续7 d。采用氯化乙酰胆碱法测定气道阻力;流式细胞术测定各组肺泡灌洗液中细胞数量、种类变化;苏木素-伊红(HE)染色法测定气道内皮组织形态变化;CytoTox 96法测定细胞凋亡情况;酶联免疫吸附测定法(ELISA)测定NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体、白细胞介素(IL)-1β和IL-10含量表达;蛋白免疫印迹法(Western blot)检测各组肺泡支气管组织磷酸化(p)-PI3K/p-Akt水平。结果:与空白组比较,模型组细胞总数、巨噬细胞总数、嗜酸性粒细胞总数、淋巴细胞总数、中性粒细胞总数明显提高(P<0.05);HE染色显示,大鼠气道黏膜水肿明显,炎症细胞大量浸润(P<0.05);细胞凋亡率明显升高(P<0.05);炎性小体NLRP3、IL-1β、IL-10含量明显上升(P<0.05);p-PI3K/p-Akt明显增高(P<0.05)。与模型组比较,青蒿素低、中、高浓度干预后,细胞总数、巨噬细胞总数、嗜酸性粒细胞总数、淋巴细胞总数、中性粒细胞总数明显下降(P<0.05);HE染色显示大鼠气道黏膜水肿程度减轻,炎症细胞浸润面积大幅减少(P<0.05);细胞凋亡率明显降低(P<0.05);炎性小体NLRP3、IL-1β、IL-10含量明显下降(P<0.05);p-PI3K/p-Akt水平显著降低(P<0.05)。结论:青蒿素可显著抑制NLRP3炎症小体激活并减少细胞焦亡,降低炎性细胞表达,可减轻哮喘大鼠的气道炎症表现及气道重塑,可能与p-PI3K/p-Akt调控有关,可为青蒿素治疗支气管哮喘提供实验依据。 展开更多
关键词 青蒿素 哮喘 气道炎症 气道重塑 磷脂酰肌醇3-激酶(pi3k)/蛋白激酶b(akt)信号通路
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