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AngⅡ上调TRPC6、NFAT2介导2型糖尿病肾病足细胞损伤 被引量:5
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作者 李明慧 马瑞霞 +2 位作者 阎文静 张岩 王莹 《青岛大学学报(医学版)》 CAS 2019年第3期299-302,307,共5页
目的 探讨瞬时受体电位阳离子通道蛋白6(TRPC6)、活化T细胞核因子2(NFAT2)参与血管紧张素Ⅱ(AngⅡ)介导的2型糖尿病肾病足细胞损伤的可能机制。方法 制备2型糖尿病大鼠模型,随机分为糖尿病组(DM组,n=11)、缬沙坦组(ARB组,n=11),同时设... 目的 探讨瞬时受体电位阳离子通道蛋白6(TRPC6)、活化T细胞核因子2(NFAT2)参与血管紧张素Ⅱ(AngⅡ)介导的2型糖尿病肾病足细胞损伤的可能机制。方法 制备2型糖尿病大鼠模型,随机分为糖尿病组(DM组,n=11)、缬沙坦组(ARB组,n=11),同时设置正常对照组(NC组,n=10),ARB组给予缬沙坦40mg/(kg·d)灌胃,DM组及NC组给予等量生理盐水灌胃,干预12周后检测各组尿清蛋白排泄率(UAE),光镜、电镜下观察肾脏及足细胞病理改变,Western blot方法测定AngⅡ、NFAT2及TRPC6蛋白的表达水平。结果 DM组UAE显著高于NC组(F=261.834,t=22.80,P<0.01),ARB组UAE水平显著低于DM组(t=13.08,P<0.01)。光镜下可见,DM组较NC组肾小球体积增大、肾基底膜增厚、系膜细胞及系膜基质增生;电镜下可见,DM组足细胞数量减少,足突融合、消失,ARB组上述病变较DM组明显减轻。与NC组相比,DM组AngⅡ、NFAT2、TRPC6蛋白表达水平均显著升高(F=290.888~639.364,t=15.00~29.50,P<0.01),ARB组较DM组明显减低(t=22.81~34.01,P<0.01)。结论 AngⅡ可能通过上调TRPC6、NFAT2介导2型糖尿病足细胞损伤。 展开更多
关键词 糖尿病肾病 足细胞 血管紧张素Ⅱ TRPC阳离子通道 NFATC转录因子类
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Wenyang Huazhuo Fang exerts transient receptor potential cation channel subfamily C member-dependent nephroprotection in a rat model of doxorubicin-induced nephropathy 被引量:3
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作者 An Peng Dong Sheng +5 位作者 Li Xingyao Cai Zimo Ye Bingyu Zhang Aijun Shi Xingmin Wu Xili 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2020年第4期613-620,共8页
OBJECTIVE:To determine the effect of Wenyang Huazhuo Fang(WHF),a Traditional Chinese Medicine decoction,on renal function in a rat model of doxorubicin-induced nephropathy,and to elucidate the underlying mechanism.MET... OBJECTIVE:To determine the effect of Wenyang Huazhuo Fang(WHF),a Traditional Chinese Medicine decoction,on renal function in a rat model of doxorubicin-induced nephropathy,and to elucidate the underlying mechanism.METHODS:Sprague-Dawley rats were randomly divided into six groups:control,doxorubicin-nephropathy,and prednisone-treated(6.45 mg·kg^-1·d^-1)doxorubicin nephropathy groups,as well as high-(7.26 g·kg^-1·d^-1),medium-(2.42 g·kg-1·d-),and low-dose(0.81 g·kg^-1·d^-1)WHF-treated doxorubicin-nephropathy groups.The nephropathy rat model was established by two tail vein injections of doxorubicin,followed by prednisone or WHF treatment for 8 weeks.Body weights were monitored and urinary protein was measured every 2 weeks.After the end of the treatment period,the rats were euthanized.Serum biochemical indicators were determined and renal morphological alterations were assessed using histological staining.The expression of transient receptor potential cation channel subfamily C member 6(TRPC6),stromal interaction molecule 1(STIM1),and calcium release-activated calcium channel protein 1(Orai1)was detected using western blotting,and their mRNA levels were examined using quantitative real-time reverse transcription-polymerase chain reaction.RESULTS:WHF treatment was found to significantly ameliorate weight loss,proteinuria,hypoalbuminemia,and dyslipidemia in doxorubicin-nephropathy rats.The protein and mRNA levels of TRPC6,STIM1,and Orai1 were partially,but significantly suppressed by prednisone or WHF treatment.CONCLUSION:Treatment with WHF significantly ameliorates renal injury in a rat model of doxorubicin-induced nephropathy,which could be at least partially related to repression of the TRPC6 pathway. 展开更多
关键词 NEPHROPATHY Doxorubicin TRPC6 cation channel Stim1 protein rat Orai1 protein rat Wenyang Huazhuo Fang
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