高糖诱导肾小球系膜细胞Notch信号通路活化及百令提取液的干预作用  

Effect of high glucose on the Notch signal pathway in mesangial cells and intervention of the cordyceps sinensis

作　　者：徐艳艳[1,2] 范秋灵[1] 丁红[1] 卢新星[1] 汪旭[1] 王力守[1] 

机构地区：[1]中国医科大学附属第一医院肾内科,沈阳110001 [2]中国医科大学附属第四医院肾内科

出　　处：《中华肾脏病杂志》2016年第2期132-137,共6页Chinese Journal of Nephrology

基　　金：国家自然科学基金（81270808）;辽宁省科技厅社会发展攻关计划（2012225019）;辽宁省高等学校重大科技平台免疫皮肤病学重点实验室自主创新课题基金（201303）

摘　　要：目的探讨高糖对肾小球系膜细胞内Notch信号通路、转化生长因子β（TGF-β）及纤维连接蛋白（FN）表达的影响及百令提取液的作用，以进一步阐明百令提取液的肾保护的作用机制。方法将大鼠肾小球系膜细胞（HBZY-1）分为5组：正常对照组（5．5mmol／L葡萄糖）、高渗透浓度对照组（5．5mmol／L葡萄糖＋19．5mmol／L甘露醇）、高糖组（25．0mmol／L葡萄糖）、Notch抑制剂DAPT组（25．0mmol／L葡萄糖＋1μmol／LDAPT）和百令提取液干预组（25．0mmol／L葡萄糖＋10mg／L百令提取液）。采用MTT法检测各组细胞增殖能力，Western印迹和实时定量PCR法分别检测Notch信号通路相关分子（Notchl、Jaggedl、Hesl）、TGF-β及FN的蛋白和mRNA表达。结果与正常对照组比较，高糖组HBZY-1细胞增殖显著增加，细胞内Notch信号相关分子（Notchl、Jaggedl、Hesl）mRNA和蛋白表达均显著上调，TGF-β、FN的mRNA和蛋白表达均显著增加（均P〈0．05）。与高糖组比较，DAPT组和百令提取液干预组HBZY-1细胞增殖均显著降低，Notch信号相关分子（Notchl、Jaggedl、Hesl）、TGF-β和FN的mRNA和蛋白表达均显著降低（均P〈0．05）。结论百令提取液可能通过抑制Notch信号通路和TGF-β通路异常活化，降低高糖诱导系膜细胞增殖，减少细胞外基质聚积，从而发挥肾脏保护作用。Objective To investigate the expression of Notch signaling molecules, transforming growth factor-β （TGF-β） and fibronectin （FN） in mesangial cell induced by high glucose, and the underlying mechanism of cordyceps sinensis. Methods Rat glomerular mesangial cells were divided into following groups： normal control group （5.5 mmol/L glucose）, hypertonic control group （5.5 mmoFL glucose＋ 19.5 mmol/L mannitol）, high glucose group （25.0 mmol/L glucose）, DAPT inhibitor group （25.0 mmol/L glucose ＋ 1 μmol/L DAPT）, cordyceps sinensis intervention group （25.0 mmol/L glucose＋ 10 mg/L cordyceps sinensis）. Cell proliferation was detected by MTr. The protein and mRNA expression of Notch signaling molecules （Notchl, Jaggedl and Hesl）, TGF-18 and FN was detected by Western blotting and real time PCR. Results Compared with normal control group, high glucoseinduced mesangial cell proliferation, as well as the mRNA and protein expression of Notchl, Jaggedl, Hesl, TGF-β1 and FN was up-regulated in high glucose group （all P 〈 0.05）. Compared with that in high- glucose group, DAPT and cordyceps sinensis inhibited high glucose- induced mesangial cell proliferation and down-regulated the mRNA and protein expression of Notch pathway, TGF-β1 and FN （all P 〈 0.05）. Conclusion By inhibiting the abnormal activation of Notch signaling pathway and TGF- β signaling pathway, cordyceps sinensis may alleviate high glucose- induced mesangial cell proliferation and reduce extracellular matrix accumulation, thus protecting kidney.

关 键 词：糖尿病肾病 肾小球系膜细胞 信号传导 百令提取液 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]