基于ROS-NLRP3炎症小体的利拉鲁肽对糖尿病肾病大鼠肾损伤的保护作用探讨

Jun Xue, Xiuqi Ma, Xuehui Wu, Jiali He, Weiling Song, Hongju Li
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摘要

目的:研究利拉鲁肽对大鼠糖尿病肾病的影响及其调节机制:研究利拉鲁肽对大鼠糖尿病肾病的影响及其调控机制。方法采用高糖高脂饮食联合STZ构建糖尿病肾病大鼠模型,随机分为生理盐水组和利拉鲁肽组。利拉鲁肽组大鼠给予利拉鲁肽 200 μg/kg sc,正常生理盐水组大鼠给予正常生理盐水 20 mg/kg sc,每天两次,连续 4 周。正常对照组不进行任何治疗。测定大鼠体重、24 小时尿总蛋白定量(UTP)、空腹血糖(FPG)、甘油三酯(TG)、胆固醇(TC)、血尿素氮(BUN)和血清肌酐(Scr)等生化指标。HE 染色、Masson 染色和 PAS 染色用于观察肾组织的病理形态学变化。Western-blot 用于检测肾组织中 NLRP3 炎症体相关蛋白的表达。用Elisa检测血清中白细胞介素-18(IL-18)和IL-1β的水平。使用 SPSS 26.0 统计软件和 Graph Prism 9.0 软件进行分析和绘图。两组间测量数据比较采用 t 检验,多组间比较采用单因素方差分析,同组间比较采用 Tukey 检验。结果与生理盐水组相比,利拉鲁肽组的FBG、UTP、BUN、Scr、TC、TG均明显降低(P<0.01),肾小球基底膜轻度增厚,肾小管管腔轻度扩张,病变损害减轻;NLRP3、ASC、caspase-1炎性体相关蛋白表达水平降低(P<0.01),IL-18、IL-1β水平降低(P<0.01):结论:利拉鲁肽可通过ROS-NLRP3炎性体通路抑制肾组织氧化应激介导的NLRP3炎性体的活化,从而抑制炎症反应,最终起到抗糖尿病肾病肾损伤的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploration on the protective effect of liraglutide on renal injury in diabetic nephropathy rats based on ROS-NLRP3 inflammasomes
Objective: To investigate the effect of liraglutide on diabetic nephropathy in rats and its regulatory mechanism. Methods: The diabetic nephropathy rat model was constructed with high-glucose-high-fat diet in combination with STZ, and was randomly divided into normal saline group and liraglutide group. The rats in liraglutide group were given sc 200 μg/kg of liraglutide, and the rats in normal saline group were given sc 20 mg/kg of normal saline twice a day for 4 weeks. The normal control group was not treated with any treatment. The biochemical indexes such as rat body weight, 24-hour urine total protein quantification (UTP), fasting blood glucose (FPG), triglyceride (TG), cholesterol (TC), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured. HE staining, Masson staining and PAS staining were used to observe the pathologically morphological changes in renal tissues. Western-blot was used to detect the expression of NLRP3 inflammasome-related protein in renal tissues. Elisa was used to measure the serum levels of interleukin-18 (IL-18) and IL-1β. SPSS 26.0 statistical software and Graph Prism 9.0 software were used for analysis and mapping. The t-test was used for the comparison of measurement data between two groups, one-way ANOVA was used for the comparison among multiple groups, and Tukey’s test was used for the comparison in the same group. Results: Compared with the normal saline group, FBG, UTP, BUN, Scr, TC and TG in the liraglutide group were significantly decreased (p < .01), the glomerular basement membrane was slightly thickened, with the tubular lumen slightly dilated and the lesion damage alleviated; the expression levels of NLRP3, ASC and caspase-1 inflammasome-related proteins were decreased (p < .01), and the levels of IL-18 and IL-1β were decreased (p < .01).Conclusion: Liraglutide can inhibit the activation of NLRP3 inflammasome mediated by oxidative stress in renal tissues through ROS-NLRP3 inflammasome pathway, thereby inhibiting the inflammation, and finally playing an anti-diabetic nephropathy renal injury role.
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