减重手术通过激活PPARα抑制氧化应激改善糖尿病大鼠肾功能  

Weight-loss surgery improves kidney function in diabetic rats by activating PPARα to suppress oxidative stress

作　　者：江宏伟[1] 王翠 周勇[1] JIANG Hong-wei;WANG Cui;ZHOU Yong(The Fourth General Surgery Department,the Fourth Affiliated Hospital of China Medical University,Shenyang 110032,China)

机构地区：[1]中国医科大学附属第四医院第四普通外科,辽宁沈阳110032

出　　处：《解剖科学进展》2020年第4期429-433,共5页Progress of Anatomical Sciences

基　　金：辽宁省自然基金(L2013318)。

摘　　要：目的探讨减重手术对糖尿病大鼠肾损伤的保护作用及其可能的作用机制。方法 SPF级SD大鼠45只,随机分为假手术组(Sham组)、糖尿病肾损伤模型组(DN组)及减重手术干预组(DJB组)。除Sham组外,其余两组大鼠建立糖尿病肾损伤模型,模型成功后DJB组大鼠给予减重手术治疗;生化检测血清肌酐(Scr)和尿素氮(BUN)含量;HE染色观察肾脏组织病理学变化;ELISA检测大鼠肾组织中超过氧化物歧化酶(SOD)与活性及丙二醛(MDA)含量;TUNEL染色观察肾组织细胞凋亡情况;免疫荧光染色检测肾组织过氧化物酶体增殖物激活受体α(PPARα)表达情况;Western blot法检测PI3K/Akt信号通路相关蛋白PI3K、Akt及pAkt的表达。结果经减重手术干预后,与DN组相比,DJB组大鼠Scr、BUN表达明显下降(P<0.05),肾脏损伤明显减轻,SOD活性升高而MDA含量降低(P<0.05);肾脏细胞凋亡数量降低且PPARα表达增加(P<0.05);减重手术干预后,大鼠肾脏组织中PI3K及p-Akt表达明显升高(P<0.05)。结论减重手术可以有效减轻糖尿病大鼠肾功能损伤,其作用机制可能与激活PPARα、抑制氧化应激有关。Objective To explore the protective effect of weight-loss surgery on kidney injury in diabetic rats and its possible mechanism. Methods Forty-five SPF SD rats were randomly divided into sham operation group(Sham group), diabetic kidney injury model group(DN group) and weight-loss surgery intervention group(DJB group).Except for the Sham group, the remaining two groups of rats established a diabetic kidney injury model. After the model was successful, the DJB group rats were given weight-loss surgery;The levels of serum creatinine(Scr) and urea nitrogen(BUN) content was detected;the histopathological changes of the kidney was observed by HE staining;Superoxide dismutase(SOD) activity and malondialdehyde(MDA) content in rat kidney tissue was detected by ELISA;The apoptosis of kidney tissue was observed by TUNEL staining;The expression of peroxisome proliferator-activated receptor α(PPARα) in kidney was detected by immunofluorescence staining;The expression of PI3 K/Akt signaling pathway related proteins PI3 K, Akt and p-Akt was detected by Western blot. Results Morris water maze results showed that compared with the control group, the escape latency was increased in the model group, the number of crossing platforms were decreased, and the target quadrant residence time was decreased. In the electroacupuncture and drug group, the escape latency of mice was decreased, the number of crossing platforms were increased, and the target quadrant stayed longer. Nesting results showed that the nesting scores of the model group were significantly lower than those of the control group, and the nesting scores of the mice in the electroacupuncture and drug groups were significantly increased. In the electroacupuncture and drug group, the neurons in the hippocampus of the mice were arranged neatly and the number of Nissl bodies were increased, and the expressions of SYN, PSD95 and GAP43 protein were increased. In addition, the expressions of p-CREB and BDNF protein in the electroacupuncture and drug groups were increased compar

关 键 词：糖尿病肾病 减重手术 氧化应激 细胞凋亡 PI3K/AKT信号通路 

分 类 号：R587.2[医药卫生—内分泌]