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Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats
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作者 YAO Wenhui TAO Rongpin +1 位作者 WANG Kai DING Xuansheng 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2024年第4期293-306,共14页
Icariin, a flavonoid glycoside, is extracted from Epimedium. This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related i... Icariin, a flavonoid glycoside, is extracted from Epimedium. This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related inflammation and exploring its potential mechanisms. The impact of icariin on vascular dysfunction was assessed in streptozotocin (STZ)-induced diabetic rats through vascular reactivity studies. Western blotting and immunofluorescence assays were performed to measure the expressions of target proteins. The release of HMGB1 and pro-inflammation cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that icariin administration enhanced acetylcholine-induced vasodilation in the aortas of diabetic rats. It also notably reduced the release of pro-inflammatory cytokines, including interleukin-8 (IL-8), IL-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). The results also unveiled that the pro-inflammatory cytokines in the culture medium of HUVECs could be increased by rHMGB1. The increased release of HMGB1 and upregulated expressions of HMGB1-related inflammatory factors, including advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), and phosphorylated p65 (p-p65) in diabetic rats and HG-induced HUVECs, were remarkably suppressed by icariin. Notably, HMGB1 translocation from the nucleus to the cytoplasm in HUVECs under HG was inhibited by icariin. Meanwhile, icariin could activate G protein-coupled estrogen receptor (GPER) and sirt1. To explore the role of GPER and Sirt1 in the inhibitory effect of icariin on HMGB1 release and HMGB-induced inflammation, GPER inhibitor and Sirt1 inhibitor were used in this study. These inhibitors diminished the effects of icariin on HMGB1 release and HMGB1-induced inflammation. Specifically, the GPER inhibitor also negated the activation of Sirt1 by icariin. These findings suggest that icariin activates GPER and increases the expression of Sirt1, which in turn reduces HMGB1 translocation and release, thereby improving vascular endothelial function in type 1 diabetic rats by inhibiting inflammation. 展开更多
关键词 ICARIIN Diabetes INFLAMMATION vascular endothelial dysfunction GPER HMGB1
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Effect of Serum from Overfatigue Rats on JNK/c-Jun/HO-1 Pathway in Human Umbilical Vein Endothelial Cells and the Intervening Effect of Tongxinluo(通心络)Superfine Powder 被引量:5
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作者 梁俊清 徐海波 +4 位作者 吴以岭 孙士然 贾振华 魏聪 游佳华 《Chinese Journal of Integrative Medicine》 SCIE CAS 2009年第2期121-127,共7页
Objective:To cultivate human umbilical vein endothelial cells (HUVECs) in the serum of overfatigue rats with the intervention of Tongxinluo (通心络) superfine powder (TXLSP).By examining the variation of the activity ... Objective:To cultivate human umbilical vein endothelial cells (HUVECs) in the serum of overfatigue rats with the intervention of Tongxinluo (通心络) superfine powder (TXLSP).By examining the variation of the activity of JNK/c-Jun/HO-1 pathway,the possible mechanisms of vascular endothelial dysfunction under overfatigue conditions and the intervening effect of TXLSP were explored.Methods:The HUVECs were randomly divided into the normal control group,the model group,the SP600125 (a specific antagonist of JNK)gro... 展开更多
关键词 overfatigue SERUM vascular endothelial dysfunction signal conduction Tongxinluo superfine powder
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Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats 被引量:3
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作者 Yue Zhang Dong-ling Zhong +5 位作者 Ya-ling Zheng Yu-xi Li Yi-jie Huang Yi-jing Jiang Rong-jiang Jin Juan Li 《Journal of Integrative Medicine》 SCIE CAS CSCD 2022年第5期432-441,共10页
Objective To investigate the influence of electroacupuncture(EA)on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)signaling pathway in spontaneously hyperten... Objective To investigate the influence of electroacupuncture(EA)on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)signaling pathway in spontaneously hypertensive rats(SHRs).Methods Eight Wistar-Kyoto rats were used as the healthy blood pressure(BP)control(normal group),and 32 SHRs were randomized into model group,EA group,EA plus ghrelin group(EA+G group),and EA plus PF04628935 group(a potent ghrelin receptor blocker;EA+P group)using a random number table.Rats in the normal group and model group did not receive treatment,but were immobilized for 20 min per day,5 times a week,for 4 continuous weeks.SHRs in the EA group,EA+G group and EA+P group were immobilized and given EA treatment in 20 min sessions,5 times per week,for 4 weeks.Additionally,1 h before EA,SHRs in the EA+G group and EA+P group were intraperitoneally injected with ghrelin or PF04628935,respectively,for 4 weeks.The tail-cuff method was used to measure BP.After the 4-week intervention,the rats were sacrificed by cervical dislocation,and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of ghrelin,nitric oxide(NO),endothelin-1(ET-1)and thromboxane A2(TXA2)in the serum.Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation.Western blot was used to measure the expression of PI3K,Akt,phosphorylated Akt(p-Akt)and eNOS proteins in the abdominal aorta.Further,quantitative real-time polymerase chain reaction(qRT-PCR)was conducted to measure the relative levels of mRNA expression for PI3K,Akt and eNOS in the abdominal aorta.Results EA significantly reduced the systolic BP(SBP)and diastolic BP(DBP)(P<0.05).HE staining showed that EA improved the morphology of the vascular endothelium to some extent.Results of ELISA indicated that higher concentrations of ghrelin and NO,and lower concentrations of ET-1 and TXA2 were present in the EA group(P<0.05).The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group.Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K,p-Akt/Akt and eNOS proteins,as well as expression levels of PI3K,Akt and eNOS mRNAs(P<0.05).In the EA+G group,SBP and DBP decreased(P<0.05),ghrelin concentrations increased(P<0.05),and the concentrations of ET-1 and TXA2 decreased(P<0.05),relative to the EA group.In addition,the levels of PI3K and eNOS proteins,the p-Akt/Akt ratio,and the expression of PI3K,Akt and eNOS mRNAs increased significantly in the EA+G group(P<0.05),while PF04628935 reversed these effects.Conclusion EA effectively reduced BP and protected the vascular endothelium,and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway. 展开更多
关键词 ELECTROACUPUNCTURE Hypertension vascular endothelial dysfunction GHRELIN PI3K/Akt/eNOS signaling pathway
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