机构地区:[1]天津市中西医结合急腹症研究所,天津300100 [2]天津市南开医院心血管内科,天津300100
出 处:《中国中医基础医学杂志》2019年第8期1059-1062,1069,共5页JOURNAL OF BASIC CHINESE MEDICINE
基 金:国家自然科学基金青年基金项目(81503409)-基于ROS介导的Akt,MAPK信号通路探讨冬虫夏草预防糖尿病大鼠对比剂肾病的作用机制
摘 要:目的:探讨冬虫夏草对糖尿病对比剂肾病(contrast-induced nephropathy, CIN)大鼠肾细胞中线粒体凋亡途径的影响。方法:大鼠按随机数字表法分为正常组、模型组、低剂量组、中剂量组和高剂量组,各组大鼠分别给予相应剂量冬虫夏草和生理盐水灌胃连续7 d,第8天大鼠经尾静脉注射碘克沙醇建立CIN模型,收集标本测定BUN、Scr、NGAL、KIM-1、NO、SOD、MDA和T-AOC,荧光定量PCR和WB法检测Caspase-3、Caspase-9、Bax和Bcl-2基因和蛋白水平,Tunel法检测肾细胞凋亡情况,HE染色法观察肾组织病理变化。结果:与正常组比较,模型组大鼠BUN、Scr、NGAL、KIM-1和MDA水平升高、NO、SOD和T-AOC水平降低,Caspase-3、9和Bax表达升高、Bcl-2及Bcl-2/Bax比值降低,肾凋亡细胞明显增多;肾细胞出现空泡、坏死等表现。与模型组比较,低剂量组Scr和MDA含量降低,Caspase-3和Bax表达降低,而Bcl-2和Bcl-2/Bax比值升高,中、高剂量组Scr、BUN、NGAL、KIM-1和MDA水平降低、NO和SOD含量升高,Caspase-3、9和Bax表达降低、Bcl-2与Bcl-2/Bax比值均升高,高剂量组大鼠肾凋亡细胞明显减少,且肾小管病理性改变减少。结论:冬虫夏草可增强糖尿病CIN大鼠抗氧化应激能力,调控线粒体凋亡途径,减少肾细胞凋亡,保护肾损伤,高剂量冬虫夏草疗效更佳。Objective: To investigate the effect of Cordyceps on regulating mitochondrial apoptosis pathway in diabetic contrast-induced nephropathy rats. Methods: All rats were divided into normal group, contrast-induced nephropathy group, low-dose Cordyceps group, medium-dose Cordyceps group and high-dose Cordyceps group. After 9 weeks, the rats were fed with Cordyceps or saline for 7 d. On the 8 th day, the rats were injected iodixano1 through tail vein to induce a CIN model. The samples were collected to test BUN, Scr, NGAL, KIM-1, NO, SOD, MDA, T-AOC. The levels of caspase-3, caspase-9, Bax and Bcl-2 gene or protein were measured by fluorescence qPCR and Western Blotting. Tunel was used to detect the apoptosis of renal cells. HE staining was used to observe the pathological changes of renal tissue. Results: Compared with the normal group, the levels of Scr, BUN, NGAL, KIM-1 and MDA increased, NO,SOD and T-AOC decreased in the model group;caspase-3, 9 and Bax expression levels were increased, Bcl-2 and Bcl-2/Bax were decreased;Apoptotic cells increased significantly, and vacuoles and necrosis were found. In the low-dose group, Scr and MDA levels decreased;caspase-3 and Bax levels decreased, meanwhile Bcl-2 and Bcl-2/Bax increased. In medium and high-dose group, the levels of Scr, BUN, NGAL, KIM-1 and MDA decreased, but NO and SOD increased;and caspase-3, 9 and Bax levels decreased, while Bcl-2 and Bcl-2/Bax increased. Caspase-3, 9 and Bax gene levels were decreased, but Bcl-2 levels and Bcl-2/Bax ratio were significantly increased. In high-dose group, the number of apoptotic cells was decreased and pathological changes of renal tubules were improved. Conclusion: The high-dose Cordyceps can enhance the ability of anti-oxidative stress and inhibit the important factors of mitochondrial apoptosis pathway to reduce renal cell apoptosis and protect renal injury for diabetic CIN rats.
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