Yiqi Tongluo capsule has protective effects against non-alcoholic fatty liver disease via regulating PI3K/AKT signaling

Background:Oxidative stress is one of the key elements in the progression of non-alcoholic fatty liver disease(NAFLD),and Yiqi Tongluo capsule(YTC)have a variety of physiological activities which include antioxidant.The purpose of this investigation was to discover the potential mechanisms of YTC ameliorates NAFLD.Methods:In this investigation,a high-fat diet(HFD)was adopted to establish a NAFLD mouse model.Liver samples were stained for oil red O and hematoxylin and eosin staining.The levels of total cholesterol(TC),triglyceride(TG),malondialdehyde(MDA),and superoxide dismutase(SOD)in the tissues were also detected.Network pharmacology was analyzed to filter out the key ingredients and targets of effect of YTC for the therapy of NAFLD.Subsequently,free fatty acids(FFA)was applied to induce Aml12 cells for in vitro experiments,and the cell samples were stained with oil red O and assayed for TC,TG,MDA,and SOD contents.At last,the Western blot technique was used to illuminate the pathway by which YTC plays a protective role against NAFLD.Results:Histopathological results demonstrated that YTC ameliorated tissue damage in the HFD-induced mouse model.At the same time,it also reduced the contents of TC,TG,MDA and increased the expression of SOD in the liver tissue of NAFLD mouse model.All of these findings demonstrate that YTC can play a role in the treatment of NAFLD by ameliorating oxidative stress.Network analysis of YTC ameliorates NAFLD mainly by modulating the PI3K-Akt signaling pathway.Follow-up in vitro experiments revealed that FFA caused lipid accumulation in Aml12 cells,which was dramatically reduced by YTC.Meanwhile,YTC could remarkably reduce the FFA-induced elevation of TC,TG,and MDA contents,and reverse the FFA-induced reduction of SOD contents.Western blot was verified for the PI3K-Akt signaling pathway.It was found that FFA could remarkably decrease the expression of p-PI3K,p-Akt,and p-GSK-3βproteins,which could be significantly increased after YTC treatment.Conclusions:The combination of network analysis prediction and experimental verification was used to identify the therapeutic effect of YTC on NAFLD.The protective effect was achieved by YTC through upregulation of PI3K-Akt-GSK-3βpathway.

Mechanism of Qiliqiangxin capsule on the regulation of IP3Rs/GRP75/VDAC1 gene in myocardial infarction rat heart

Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left anterior descending coronary artery.After operation,the rats were randomly assigned to the model group,the Qiliqiangxin group and the captopril group;a sham-operated group was also available as a control.After four weeks of treatment,the extent of infarction in rats was observed by gross cardiac structure and the morphological changes of myocardial histopathology were observed by HE staining.Detection of mitochondrial Ca^(2+)transport-related genes such as inositol-1,4,5-trisphosphate receptor 2(IP3R2),glucose regulated protein 75(GRP75),voltage-dependent anion channel 1(VDAC1),and mitofusion 2(Mfn2)and mitochondrial apoptosis-related genes such as B-cell lymphoma-2(Bcl-2)and Bcl-2 related X protein(Bax)mRNA expression changes was measured by RT-PCR in the infarct margins of the heart;Western blot was used to detect changes in Bcl-2,Bax protein expression in myocardial tissue.The rate of apoptosis in cardiac myocardial tissue was detected by TUNEL staining.Results:Compared with the sham group,the anterior left ventricular wall of the model group showed a large area of infarction,and the structure of myocardial tissue was disordered.The mRNA expression level of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly increased(P<0.05,P<0.01);The mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were significantly decreased(P<0.01),while the mRNA and protein expression of Bax were significantly increased(P<0.01);and apoptosis rate was significantly increased(P<0.01).Compared with the model group,the infarct size of cardiac gross specimens in the Qiliqiangxin group and the captopril group was reduced and myocardial fibers were relatively well ordered;The mRNA expression of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly reduced(P<0.01);the mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were increased(P<0.05,P<0.01),and the mRNA and protein expression of Bax were significantly decreased(P<0.05,P<0.01).and apoptosis rate was significantly decreased(P<0.01).Conclusion:Qiliqiangxin Capsule can improve the morphological structure of the heart of rats with MI,and its mechanism is related to regulation of the gene expression of mitochondrial Ca^(2+)transport complex IP3R2/GRP75/VDAC1,thereby inhibiting apoptosis.

PillCam~ SB3 capsule: Does the increased frame rate eliminate the risk of missing lesions?

Since its emergence in 2000, small bowel capsule endoscopy(SBCE) has assumed a pivotal role as an investigation method for small bowel diseases. The PillCam SB2-ex offers 12 h of battery time, 4 more than the previous version(SB2). Rahman et al recently found that the PillCam SB2-ex has a significantly increased completion rate, although without higher diagnostic yield, compared with the SB2. We would like to discuss these somewhat surprising results and the new potentialities of the PillCam SB3 regarding the diagnostic yield of small bowel studies. PillCam SB3 offers improved image resolution and faster adaptable frame rate over previous versions of SBCE. We recently compared the major duodenal papilla detection rate obtained with PillCam SB3 and SB2 as a surrogate indicator of diagnostic yield in the proximal small bowel. The PillCam SB3 had a significantly higher major duodenal papilla detection rate than the PillCam SB2(42.7% vs 24%, P = 0.015). Thus, the most recent version of the PillCam capsule, SB3, may increase diagnostic yield, particularly in the proximal segments of the small bowel.

基于Mascot Capsule技术的3D手机游戏开发

概述手机游戏的开发现状和Mascot Capsule(也称作Micro3D)的简单介绍,重点介绍Mascot Capsule和JSR-184的区别,Mascot Capsule技术3D游戏架构的搭建,一个简单3D手机游戏开发的介绍。

Prediction and validation of molecular biological mechanism of Fuzheng Huayu capsule in the treatment of liver cancer

Background:Fuzheng Huayu capsule(FZHY)combined with antiviral treatment has been shown to significantly reduce the risk of liver cancer in patients with hepatitis B cirrhosis.However,the potential of FZHY to directly treat liver cancer remains largely unknown.This study aims to investigate the molecular mechanism underlying the potential of FZHY in treating liver cancer.Methods:A network pharmacological analysis was performed using the Traditional Chinese Medicine Systems Pharmacology database to identify FZHY compounds and targets.Disease targets were searched using the Genecards database,and transcriptome data was downloaded from the NCBI database.Gene Ontology analysis was conducted using the DAVID database,and Kyoto Encyclopedia of Genes and Genomes analysis was based on KOBAS and bioinformatics methods.The Swissdock database was used for molecular docking.In cell experiments,the half inhibitory concentration(IC50)of FZHY was determined using the CCK8 method.The effects of FZHY on cell viability,apoptosis,and mitochondrial membrane potential were evaluated using a fluorescence microscope and flow cytometry.The molecular mechanism of FZHY in treating liver cancer was verified using quantitative polymerase chain reaction.Results:A total of 127 compounds and 184 proteins were identified as potential active ingredients and putative liver cancer-related targets.Additionally,1,899 liver cancer targets,279 transcriptome targets,and 3 pathways(p53 signaling pathway,apoptosis and PI3K-Akt pathway)were collected.The FZHY-targets-liver cancer interaction network was constructed.IC50 of FZHY lyophilized powder solution to liver cancer was 5.13 mg/mL(IC50=5.13 mg/mL).FZHY treatment led to an increase in the ratio of cell apoptosis and induced mitochondrial membrane potential damage,resulting in an increase in the number of dead cells.The expression levels of CCNB1 and BIRC5 were induced with FZHY treatment,while the expression levels of AKR1C3 and IGF2 were reduced.Conclusion:FZHY promotes apoptosis of liver cancer cells by acting on the p53 signaling pathway,apoptosis,and PI3K-Akt pathway.CCNB1,BIRC5,AKR1C3,and IGF2 are potential target proteins for FZHY in treating liver cancer.

Effect of Xifeng Capsule on blood stasis in patients with rheumatoid arthritis by regulating miR-126-VEGF/PI3K/AKT signaling pathway

Objective:From the perspective of miR-126-vascular endothelial cytokine(VEGF)/phosphatidylinositol 3-kinase(PI3K)/ser-threonine protein kinase(AKT)signaling pathway,Xinfeng Capsule(XFC)can improve rheumatoid arthritis(RA))The mechanism of the patient's blood stasis state.Methods:Sixty RA patients meeting the diagnostic criteria were selected and divided into XFC treatment group 30 cases and Leflunomide(LEF)control group 30 cases according to the random number table method.The treatment group took Xinfeng Capsules(3 capsules each time,3 times/d),and the control group took Leflunomide(1 capsule each time,1 times/d).Observe the blood stasis symptom scores of RA patients,and detect the laboratory indicators erythrocyte sedimentation rate(ESR),c-reactive protein(CRP),rheumatoid factor(RF),anti-cyclic citrullinated peptide antibody(CCP),thrombin time(TT),part prothrombin time(APTT),prothrombin time(PT),D dimer(DD),fibrinogen(FBG),platelets(PLT),mean platelet volume(MPV),platelet distribution width(PDW)levels.Real-time fluorescent quantitative PCR method was used to detect the level of miR-126,and the ELISA method was used to detect the levels of tumor necrosis factor(TNF-α),interleukin-6(IL-6),IL-35,VEGF,PI3K,and AKT.Spearman method was used to analyze the correlation between the total score of blood stasis symptoms,blood stasis-related indicators and disease activity indicators,cytokines,miR-126,VEGF,PI3K,and AKT in RA patients.Results:Comparing the two groups after treatment,the XFC group improved blood stasis symptoms,disease activity indicators,decreased miR-126,VEGF,PI3K,AKT,TNF-α,IL-6,D-D,FBG,PLT,and increased IL-35 The level was significantly better than the LEF group,with statistical significance(P<0.05,P<0.01).Correlation analysis showed that there was a certain correlation between the total score of blood stasis symptoms,blood stasis related indicators and disease activity indicators,cytokines,miR-126,VEGF,PI3K,and AKT in RA patients.Conclusion:There is blood stasis in RA patients.XFC may improve the cytokine network disorder of patients through miR-126-VEGF/PI3K/AKT signaling pathway,thereby improving the blood stasis status of RA patients.

Effects of Liancao-Xieli capsule on intestinal mucosal inflammatory factors and TLR4/PI3K/Akt/mTOR signaling pathway in mice with ulcerative colitis

Objective:To observe the effect of Liancao-Xieli capsule on intestinal mucosal inflammatory factors and TLR4/PI3K/Akt/mTOR signaling pathway in mice with ulcerative colitis(UC);Methods:40 male C57BL/6 mice were randomly divided into the control group,model group,Liancao-Xieli group and mesalazine group,with 10 mice in each group.In addition to the control group,the remaining three groups of mice were induced by 3%dextran sulfate sodium(DSS)to induce acute UC model.During the modeling period,mice in each group were given corresponding drugs and normal saline by gavage.At the end of the experiment,HE staining was used to observe the pathological changes of colonic tissue in each group,and ELISA was used to detect the inflammatory factors(TNF-α,IL-6,IL-1β,IL-8,IL-17,and INF-γ)in serum and colonic tissue.The expression levels of TLR4/PI3K/Akt/mTOR signaling pathway related proteins were also detected by Western blot;Results:Compared with the model group,Liancao-Xieli capsule could significantly increase the colon length and decrease the score of colon histopathology in UC mice(P<0.01).In addition,the levels of TNF-α,IL-6,IL1β,IL-8,IL-17,and INF-γwere significantly reduced in serum and colon tissue,and the expressions of TLR4,PI3K,p-Akt and p-mTOR were significantly down-regulated in LiancaoXieyi group when compared with the model group(P<0.01).While the expressions of Akt and mTOR were not significantly affected in Liancao-Xieyi group(P>0.05);Conclusion:LiancaoXieli capsule can reduce the secretion of inflammatory factors,improve the intestinal mucosal damage and inflammatory response in UC by inhibiting the activation of TLR4/PI3K/Akt/mTOR signaling pathway。

当贡-3胶囊联合盐酸替罗非班注射液治疗气虚血瘀证不稳定型心绞痛的疗效观察

目的探究当贡-3胶囊联合盐酸替罗非班注射液治疗气虚血瘀证不稳定型心绞痛的治疗效果。方法选取内蒙古自治区中医医院2018年1月至2021年6月医治的不稳定型心绞痛病人120例,按随机数字表法分为两组各60例,对照组用盐酸替罗非班注射液治疗,试验组用当贡-3胶囊联合盐酸替罗非班注射液治疗。对两组病人的治疗效果、心绞痛发作情况、炎症水平、血脂水平、不良心血管事件发生情况进行比较分析。结果试验组整体疗效及治疗总有效率显著高于对照组(P<0.05)。治疗后,两组病人的心绞痛发作次数减少,持续时间缩短,肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)水平下降,白细胞介素-10(IL-10)水平升高,且试验组心绞痛发作次数、持续时间、TNF-α、CRP水平[(0.72±0.14)次、(2.47±0.48)min、(17.49±3.48)ng/L、(2.19±0.42)mg/L]显著低于对照组[(0.91±0.18)次、(3.24±0.64)min、(19.42±3.88)ng/L、(2.71±0.54)mg/L],IL-10水平显著高于对照组(P<0.05)。治疗后,两组病人三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)水平下降,高密度脂蛋白(HDL-C)水平升高,试验组TG、TC、LDL-C水平低于对照组,HDL-C水平高于对照组(P<0.05)。结论当贡-3胶囊联合盐酸替罗非班注射液治疗气虚血瘀证不稳定性心绞痛有较好疗效,能够提高治疗效果,调节病人炎症水平和血脂水平,从而缓解病人病情。

藤黄健骨胶囊联合碳酸钙D_(3)片、唑来膦酸注射液治疗老年骨质疏松症的临床效果

目的:探究藤黄健骨胶囊联合碳酸钙D_(3)片、唑来膦酸注射液治疗老年骨质疏松症(0P)的临床效果。方法:选取2020年1月—2022年12月在南昌市第三医院收治的60例老年OP患者,随机分为对照组及观察组,各30例。给予两组相应的常规治疗,对照组采用碳酸钙D_(3)片、唑来膦酸注射液治疗,观察组在对照组给药基础上另给予藤黄健骨胶囊治疗。评价对比两组临床效果、骨密度(BMD)、疼痛程度、骨代谢标志物水平及骨折发生率。结果:观察组的总有效率(96.67%)显著高于对照组(80.00%)(P<0.05)。治疗后,两组腰椎、股骨颈、Wards三角区的BMD均升高,且观察组均高于对照组(P<0.05)。治疗3、6个月后,两组视觉模拟评分法(VAS)评分均下降,且观察组均低于对照组(P<0.05)。治疗后,两组血清Ⅰ型前胶原氨基端延长肽(PⅠNP)、血清I型胶原交联C末端肽(CTX)水平均降低,且观察组均低于对照组(P<0.05)。观察组骨折发生率(6.67%)显著低于对照组(30.00%)(P<0.05)。结论:藤黄健骨胶囊联合碳酸钙D_(3)片、唑来膦酸注射液治疗老年OP疗效良好,提高患者的BMD,减轻疼痛感,降低骨代谢标志物水平及骨折发生。

荆花胃康胶囊治疗慢性萎缩性胃炎的疗效及对NLRP3通路介导炎症及焦亡的影响

目的研究荆花胃康胶囊治疗慢性萎缩性胃炎的疗效及对NOD样蛋白受体3(NLRP3通路介导炎症及焦亡的影响。方法选择2021年1月至2022年3月寿县人民医院消化内科收治的慢性萎缩性胃炎患者进行前瞻性研究,采用随机数字表分为接受荆花胃康胶囊联合西医药物治疗的观察组(n=58)和西医药物治疗的对照组(n=57)。治疗4个疗程后评价两组疗效、中医证候积分及胃黏膜病理积分,检测两组胃黏膜中NLRP3、Caspase-1的mRNA表达水平及血清中IL-1β、IL-18、GSDMD的水平。结果观察组的治疗有效率高于对照组,差异有统计学意义(P<0.05);两组治疗后的胃痛、胃痞满、嗳气泛酸、食少纳差中医证候积分,腺体萎缩、肠上皮化生、异型增生的病理积分,胃黏膜中NLRP3、Caspase-1的mRNA表达水平,血清中IL-1β、IL-18、GSDMD的水平低于治疗前,且观察组低于对照组,差异均有统计学意义(P<0.05)。结论荆花胃康胶囊治疗能够改进慢性萎缩性胃炎的治疗效果,改善中医证候及胃黏膜病理改变,抑制NLRP3通路介导的炎症及焦亡可能是与之相关的分子机制。

No significant difference in clinically relevant findings between Pillcam~? SB3 and Pillcam~? SB2 capsules in a United States veteran population

BACKGROUND Capsule endoscopy(CE) allows for a non-invasive small bowel evaluation for a wide range of gastrointestinal(GI) symptoms and diseases. Capsule technology has been rapidly advancing over recent years, often improving image frequency and quality. The Pillcam~? SB3(SB3) capsule is one such technology that offers an adaptive frame rate advantage over the previous versions of the capsule the Pillcam~? SB2(SB2). Some have proposed that this improvement in capsule technology may lead to increased diagnostic yields; however, real world clinical data is currently lacking.AIM To evaluate the clinically relevant findings of SB3 and SB2 capsules in a population of United States veterans.METHODS A retrospective analysis of 260 consecutive CE studies was performed including130 SB3 and 130 SB2 capsule studies. Recorded variables included: age, gender,type of capsule, body mass index, exam completion, inpatient status, opioid use,diabetes, quality of preparation, gastric transit time, small bowel transit time,indication, finding, and if the exam resulted in a change in clinical management.The primary outcome measured was the detection of clinically relevant findings between SB3 and SB2 capsules.RESULTS Mean age of the study population was 67.1 ± 10.4 years and 94.2% of patients were male. Of these 28.1% were on opioid users. The most common indications for capsule procedure were occult GI bleeding(74.6%) and overt GI bleeding(14.6%). Rates of incomplete exam were similar between SB3 and SB2 groups(16.9% vs 9.2%, P = 0.066). The overall rate of clinically relevant finding was48.9% in our study. No significant difference was observed in SB3 vs SB2 capsules for clinically relevant findings(46.2% vs 51.5%, P = 0.385) or change in clinical management(40.8% vs 50.0%, P = 0.135).CONCLUSION Our study found no significant difference in clinically relevant findings between SB3 and SB2 capsules.

芪苈强心胶囊联合沙库巴曲缬沙坦钠对老年慢性心力衰竭患者血清Gal-3、Copeptin水平及TLR4/NF-κB信号通路的影响

目的:探讨芪苈强心胶囊辅助治疗老年CHF对患者Gal-3、Copeptin水平及TLR4/NF-κB信号通路的影响。方法:采用随机数表法将2021年3月至2023年3月平顶山市第一人民医院112例老年CHF患者分为采用沙库巴曲缬沙坦钠(诺欣妥)治疗的常规组(n=56例)和采用芪苈强心胶囊辅助治疗的联合组(n=56例)。观察两组疗效、心功能、血清半乳糖凝集素-3(Gal-3)、Copeptin水平、Toll样受体(TLR4)、核因子-κ(NF-κB)水平及不良反应。结果:治疗3个月后,联合组的临床治疗总有效率、心输出量(CO)、左心室射血分数(LVEF)高于常规组(P<0.05);联合组TLR4、NF-κB、Gal-3、Copeptin水平低于常规组(P<0.05);两组患者用药期间不良反应发生率对比,差异无统计学意义(P>0.05)。结论:芪苈强心胶囊联合沙库巴曲缬沙坦钠可调节TLR4、NF-κB水平,促进老年CHF患者心功能恢复,并抑制心肌重构,进而有效提高临床治疗疗效,且不增加患者不良反应发生风险。

营心宁胶囊联合辛伐他汀治疗高龄男性ASCVD的疗效及对TGF-β1-Smad2/3通路的影响

目的 研究营心宁胶囊治疗高龄男性动脉粥样硬化性心血管疾病(ASCVD)的疗效及对转化生长因子(TGF-β1)-Smad2/3通路的影响。方法 选择高龄男性ASCVD患者,随机分为对照组(辛伐他汀治疗)和联合组(营心宁胶囊联合辛伐他汀治疗)。治疗前及治疗3个月后,分别检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、高密度脂蛋白胆固醇(HDLC)、非HDLC、TGF-β1、Smad2、Smad3的水平,比较两组全因死亡及主要不良心血管事件(MACE)的情况。结果 治疗3个月后,两组TC、LDLC、非HDLC、TGF-β1、Smad2、Smad3均较治疗前降低,且联合组LDLC、非HDLC、TGF-β1、Smad2、Smad3低于对照组(P<0.05)。联合组全因死亡及MACE发生率低于对照组(P<0.05)。结论 辛伐他汀联合营心宁胶囊治疗高龄男性ASCVD,可显著降低LDLC并抑制其TGF-β1-Smad2/3通路,显著降低全因死亡及MACE发生率。

Effects of Hemp seed soft capsule on colonic ion transport in rats

AIM To investigate the effect of Hemp seed soft capsule(HSCC) on colonic ion transport and its related mechanisms in constipation rats.METHODS Sprague-Dawley male rats were randomly divided into three groups: normal group, constipation group and HSSC group. Rats in the constipation and HSSC groups were administrated loperamide 3 mg/kg per day orally for 12 d to induce the constipation model. Then, the HSSC group was given HSSC 0.126 g/kg per day by gavage for 7 d. The normal and constipation groups were treated with distilled water. After the treatment, the fecal wet weight and water content were measured. The basal short-circuit current(Isc) and resistance were measured by an Ussing Chamber. Besides the in vivo drug delivery experiment above, an in vitro drug application experiment was also conducted. The accumulative concentrations of HSSC(0.1 mg/m L, 0.5 mg/m L, 1.0 mg/m L, 2.5 mg/m L, 5.0 mg/m L, 10.0 mg/m L and 25.0 mg/m L) were added to the normal isolatedcolonic mucosa and the Isc was recorded. Further, after the application of either ion(Cl^-or HCO_3^-) substitution, ion channel-related inhibitor(N-phenylanthranilic acid, glybenclamide, 4,4-diisothiocyano-2,2-stilbenedisulfonic acid or bumetanide) or neural pathway inhibitor [tetrodotoxin(TTX), atropine, or hexamethonium], the Isc induced by HSSC was also measured. RESULTS In the constipation group, the fecal wet weight and the water content were decreased in comparison with the normal group(P < 0.01). After the treatment with HSSC, the fecal wet weight and the water content in the HSSC group were increased, compared with the constipation group(P < 0.01). In the constipation group, the basal Isc was decreased and resistance was increased, in comparison with the normal group(P < 0.01). After the treatment with HSSC, the basal Isc was increased(P < 0.05) and resistance was decreased(P < 0.01) in the HSSC group compared with the constipation group. In the in vitro experiment, beginning with the concentration of 1.0 mg/m L, differences in Isc were found between the experimental mucosa(with HSSC added) and control mucosa. The Isc of experimental mucosa was higher than that of control mucosa under the same concentration(1.0 mg/m L, P < 0.05; 2.5-25 mg/m L, P < 0.01). After the Cl^-or HCO_3^-removal and pretreated with different inhibitors(c AMPdependent and Ca^(2+)-dependent Cl^-channels, Na^+-K^+-2 Cl^-cotransporter(NKCC), Na^+-HCO_3^-cotransporter or Cl^-/HCO_3^-exchanger inhibitor), there were differences between experimental mucosa and control mucosa; the Isc of experimental mucosa was lower than that of control mucosa under the same concentration(P < 0.05). Meanwhile, after pretreatment with neural pathway inhibitor(TTX, atropine, or hexamethonium), there were no differences between experimental mucosa and control mucosa under the same concentration(P > 0.05).CONCLUSION HSSC ameliorates constipation by increasing colonic secretion, which is mediated via the coaction of c AMPdependent and Ca^(2+)-dependent Cl^-channels, NKCC, Na^+-HCO_3^-cotransporter or Cl^-/HCO_3^-exchanger.

复方蛇龙胶囊抑制Bax/Caspase-3信号通路减轻膜性肾病大鼠肾组织细胞凋亡的研究

目的 探讨复方蛇龙胶囊抑制Bax/Caspase-3信号通路减轻膜性肾病大鼠肾组织细胞凋亡的影响。方法 抽取10只6周龄SPF级雄性SD大鼠作为正常组,其余40只采用注射阳离子化牛血清白蛋白(Alb)构建膜性肾病大鼠模型,采用随机数字表法将其分为模型组,雷公藤多苷片组,复方蛇龙胶囊低、高剂量组,每组10只。除正常组和模型组灌服等量生理盐水外,其余各组灌胃给予相应药物,连续4周。HE染色、Masson染色、透射电镜及扫描电镜观察各组肾组织病理学变化;比较各组大鼠尿微量白蛋白(mAlb)和血肌酐(SCr)、甘油三酯(TG)、总胆固醇(TC)、Alb、总蛋白(TP)含量;比较各组大鼠肾组织细胞凋亡率;比较各组大鼠肾组织Nephrin、Podocin、Bcl-2、Bax和Caspase-3 m RNA表达水平。结果 与正常组比较,模型组大鼠尿m Alb含量升高(P<0.05);血清Alb、TP含量降低,TC、TG和SCr含量升高(P<0.05)。与模型组比较,复方蛇龙胶囊低、高剂量组大鼠尿m Alb含量降低(P<0.05);血清Alb、TP含量升高,TC、TG和SCr含量降低(P<0.05)。与复方蛇龙胶囊低剂量组比较,复方蛇龙胶囊高剂量组尿m Alb降低(P<0.05);血清Alb、TP含量升高,SCr含量降低(P<0.05)。正常组大鼠HE染色可见肾小球结构完整;Masson染色未见组织纤维化。模型组大鼠HE染色可见肾小球体积增大,肾小管可见空泡变性,并伴有蛋白管型;Masson染色可见组织纤维化,蓝色胶原纤维组织出现。与模型组比较,复方蛇龙胶囊低、高剂量组大鼠肾小球体积增大、肾小管空泡变性及组织纤维化有所减轻。正常组基底膜结构完整,足细胞结构正常;模型组肾小球大面积水肿,基底膜增厚,足突融合变宽,足细胞结构严重损伤,细胞骨架蛋白裸露;与模型组比较,复方蛇龙胶囊低、高剂量组大鼠基底膜增厚程度减轻,足细胞形态结构趋于正常。与正常组比较,模型组大鼠肾组织细胞凋亡率升高(P<0.05);与模型组比较,复方蛇龙胶囊低、高剂量组大鼠肾组织细胞凋亡率降低(P<0.05);与复方蛇龙胶囊低剂量组比较,复方蛇龙胶囊高剂量组大鼠肾组织细胞凋亡率降低(P<0.05)。与正常组比较,模型组大鼠Nephrin、Podocin、Bcl-2 m RNA表达水平降低,Caspase-3、Bax m RNA表达水平升高,Bcl-2/Bax比值降低(P<0.05)。与模型组比较,复方蛇龙胶囊低、高剂量组大鼠Nephrin、Podocin、Bcl-2 m RNA表达水平升高,Caspase-3、Bax m RNA表达水平降低,Bcl-2/Bax比值升高(P<0.05)。与复方蛇龙胶囊低剂量组比较,复方蛇龙胶囊高剂量组Nephrin、Podocin m RNA表达水平升高,Bcl-2/Bax比值升高(P<0.05)。结论 复方蛇龙胶囊能有效改善膜性肾病大鼠蛋白尿,显著减轻肾脏病理损伤,延缓膜性肾病进展,其机制可能与抑制足细胞凋亡有关。

Effect of Shengsui Jiangu Capsule on bone conversion in rats with alcoholic osteoporosis

Objective:To study the mechanism of Shengsui Jiangu Capsule promoting vitamin D_(3)regulating bone turnover in rats with alcoholic osteoporosis.Methods:120 SD rats were randomly divided into four groups:model group(alcoholic osteoporosis model group),blank control group,western medicine control group(calcium carbonate tablet and affa D_(3)control group),Chinese medicine experimental group(Shengsui Jiangu capsule experimental group),30 rats in each group.After 8,12 and 16 weeks,the serum levels of 25 hydroxyvitamin D_(3)(25(OH)D_(3)),1,25dihydroxyvitamin D_(3)(1,25(OH)_(2)D_(3)),cross-linked carboxy-terminal peptide of type 1 collagen(β-CTX)and N-terminal propeptide of type 1 collagen(P1NP)in rats and the density of the femur of rats were detected and compared.The correlation between vitamin D_(3)markers(25(OH)D_(3)and 1,25(OH)_(2)D_(3))and bone turnover indices(P1NP andβ-CTX)and bone mineral density was analyzed.Results:In the experimental group,bone mineral density(BMD)was significantly increased(P<0.01),bone repair and mineral stability and balance were maintained during bone turnover,the level of bone formation marker P1NP was significantly increased(P<0.01),and the level of bone resorption markerβ-CTX was significantly decreased(P<0.01).Serum levels of 25(OH)D_(3)and 1,25(OH)_(2)D_(3)were increased(P<0.01),and significantly higher than those in western medicine control group(P<0.05).Conclusion:Shengsui Jiangu capsule can effectively improve bone density in alcoholic osteoporosis(AOP)rats,and its mechanism may be related to promoting bone calcium absorption and regulating bone conversion.

基于HAT/HDAC平衡调控PPARγ/PI3K/Akt通路活化探讨黄连化浊胶囊对糖尿病大血管病变的作用

目的 探讨基于组蛋白乙酰转移酶(HAT)/组蛋白脱乙酰酶(HDAC)平衡调控过氧化物酶体增殖物激活受体γ(PPARγ)/PI3K/Akt通路活化探讨黄连化浊胶囊对糖尿病大血管病变的影响。方法 40只载脂蛋白E(ApoE)基因剔除小鼠均建立糖尿病大血管病变模型,随机分为模型组、阿托伐他汀组、黄连化浊胶囊组、阿托伐他汀+黄连化浊胶囊组,每组10只。10只野生型C57小鼠为空白组。阿托伐他汀组小鼠灌胃阿托伐他汀10 mg/kg,黄连化浊胶囊组小鼠灌胃黄连化浊胶囊0.675 g/kg,阿托伐他汀+黄连化浊胶囊组小鼠灌胃给予阿托伐他汀10 mg/kg+黄连化浊胶囊0.675 g/kg,空白组及模型组小鼠灌胃等体积生理盐水,每天1次,连续8周。培养小鼠胸主动脉平滑肌细胞,分为空白组、人氧化低密度脂蛋白(ox-LDL)组、ox-LDL+PPARγ沉默组、ox-LDL+PPARγ过表达组,除空白组采用等体积空白血清培养外,其他3组细胞均加入100μg/mL ox-LDL处理并采用含200μg/mL黄连化浊胶囊的血清共培养,ox-LDL+PPARγ沉默组进行PPARγ siRNA转染,ox-LDL+PPARγ过表达组转染PPARγ质粒。采用全自动生化分析仪检测小鼠血糖及血脂水平,H-E染色观察小鼠胸主动脉病理形态,流式细胞术检测平滑肌细胞凋亡率,蛋白质印迹法和qPCR分别检测细胞中HAT1、HDAC1、PPARγ、PI3K、Akt蛋白和mRNA的表达。结果 与模型组比较,阿托伐他汀组、黄连化浊胶囊组及阿托伐他汀+黄连化浊胶囊组小鼠餐后血糖、总胆固醇、甘油三酯及低密度脂蛋白胆固醇水平均降低,高密度脂蛋白胆固醇水平均升高(P均<0.05);与模型组相比,阿托伐他汀组、黄连化浊胶囊组小鼠主动脉血管内壁层次紊乱改善,可见少量的泡沫细胞,阿托伐他汀+黄连化浊胶囊组小鼠胸主动脉血管内壁层次紊乱改善优于阿托伐他汀组及黄连化浊胶囊组。ox-LDL+PPARγ沉默组平滑肌细胞凋亡率低于ox-LDL组和ox-LDL+PPARγ过表达组(P均<0.05);与ox-LDL组相比,ox-LDL+PPARγ沉默组平滑肌细胞中HAT1蛋白和mRNA表达均升高,而HDAC1、PPARγ、PI3K、Akt蛋白和mRNA表达均降低(P均<0.05);与ox-LDL+PPARγ沉默组相比,ox-LDL+PPARγ过表达组平滑肌细胞中HAT1蛋白和mRNA表达均降低,HDAC1、PPARγ、PI3K、Akt蛋白和mRNA表达均升高(P均<0.05)。结论 黄连化浊胶囊可能通过抑制HAT表达促进HDAC1表达和PPARγ/PI3K/Akt通路活化,抑制糖尿病大血管病变小鼠代谢紊乱,增加平滑肌细胞凋亡,减少动脉斑块形成,发挥保护作用。

Upregulation of histone H3 caused by CRYAA may contribute to the development of age-related cataract

Objective:Age-relate cataract(ARC)is a disease of the eyes with no effective drugs to prevent or treat patients.The aim of the present study is to determine whether histone H3,αA-crystallin(CRYAA),β-galactosidase(GLB1),and p53 are involved in the pathogenesis of ARC.Methods:A total of 99 anterior lens capsules(ALCs)of patients with ARC of various nuclear grades,ultraviolet models of ALCs,and two human lens epithelial cell lines(FHL-124 and SRA01/04)were used,and the expression of histone H3,CRYAA,GLB1,and p53 were detected by immunoblotting and reverse transcription and real time-quantitative polymerase chain reaction.The association between CRYAA with histone H3,GLB1,and p53 was assessed in FHL-124 and SRA01/04 cells following CRYAA overexpression.Results:Histone H3 and p53 in ALCs of patients with ARC were up-regulated in a grade-dependent manner,and the expression of CRYAA showed a positive association with histone H3,p53,and GLB1.In UV models of ALCs and human lens epithelial cell lines,the expression levels of histone H3,cell apoptosis factors(Bax/Bcl-2,cleaved caspase-3),and inflammation factors(interleukin-6,tumor necrosis factor-α)were all up-regulated.Furthermore,transfection of CRYAA in FHL-124 cells induced overexpression of histone H3.Conclusion:CRYAA-mediated upregulation of histone H3 may be involved in the pathogenesis of ARC.p53 may also have a role in ARC development,but not via the CRYAA-histone H3 axis.The results of the present study may assist in improving our understanding of the pathogenesis of ARC and in identifying potential targets for treatment.

二草清肝合剂联合多烯磷脂酰胆碱治疗非酒精性脂肪性肝病临床研究

目的:观察二草清肝合剂联合多烯磷脂酰胆碱胶囊治疗非酒精性脂肪性肝病(NAFLD)湿热蕴结证的临床疗效。方法:选取104例NAFLD湿热蕴结证患者,按随机数字表法分成对照组和治疗组,每组52例。对照组给予多烯磷脂酰胆碱胶囊治疗,治疗组在对照组基础上给予二草清肝合剂治疗。2组均治疗3个月。比较2组临床疗效、生化指标、中医证候评分、氧化应激指标。结果:治疗后,治疗组总有效率94.23%,高于对照组78.85%,差异有统计学意义(P<0.05)。治疗后,2组血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆固醇(TC)、甘油三酯(TG)水平均较治疗前降低,治疗组血清AST、ALT、TC、TG水平均低于对照组,差异均有统计学意义(P<0.05)。2组中医证候评分均较治疗前降低,治疗组中医证候评分低于对照组,差异均有统计学意义(P<0.05)。2组血清正五聚体蛋白3 (PTX3)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平均较治疗前升高,治疗组血清PTX3、SOD、GSH-Px水平均高于对照组,差异均有统计学意义(P<0.05)。结论:二草清肝合剂联合多烯磷脂酰胆碱胶囊治疗NAFLD湿热蕴结证临床疗效较好,能改善肝功能、血脂状况,缓解临床症状,减轻氧化应激反应。

舒肝解郁胶囊对抑郁模型大鼠海马神经元凋亡及脑组织caspase-3蛋白表达的影响

目的:研究舒肝解郁胶囊对抑郁模型大鼠海马神经元凋亡及脑组织caspase-3蛋白表达的影响,探讨其治疗抑郁症的作用机制。方法:将雄性SD大鼠随机分为正常对照组、模型组、舒肝解郁组和氟西汀组四组;采用慢性轻度不可预见性应激(CUMS)结合孤养建立抑郁大鼠模型,并用旷场、糖水消耗和强迫游泳试验评价大鼠的行为学改变,观察海马CA3区神经元的形态结构及凋亡,应用蛋白印记分析检测脑组织caspase-3蛋白的表达。结果:与模型组比较,舒肝解郁组大鼠自发活动显著增加;糖水消耗量、糖水偏爱率显著升高;强迫游泳不动时间显著缩短;大鼠海马CA3区细胞结构破坏显著改善,凋亡细胞数及脑组织caspase-3蛋白表达显著减少(P<0.05或0.01);氟西汀组与舒肝解郁组比较,差异无统计学意义(P>0.05)。结论:舒肝解郁胶囊能显著改善抑郁模型大鼠的抑郁症状,促进抑郁大鼠海马CA3区神经细胞损伤的修复和/或新生;减少大鼠脑组织caspase-3蛋白表达,阻止脑神经细胞的凋亡;疗效与氟西汀相当。