阿托伐他汀抑制NLRP3炎性小体缓解实验性IgA肾病大鼠肾损伤

Renal preventive mechanism of atorvastatin on with IgA nephropathy of rats

目的观察阿托伐他汀对IgA肾病大鼠的肾保护作用,探讨其介导NLRP3炎性小体的作用机制。方法 Sd大鼠随机分为对照组、模型组、阿托伐他汀低、高剂量组,每组10只;利用口服牛γ-球蛋白(BGG)联合尾静脉注射BGG方法建立IgA肾病大鼠模型;于造模完成后灌胃给予低、高剂量阿托伐他汀治疗6周;取血液分离血清检测肌酐(Scr)、尿素氮(BUN)、总蛋白(TP)、白蛋白丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)含量;检测大鼠尿液中红细胞数目及24 h尿蛋白(24 h TUP)水平;HE染色检测肾病理组织学变化;免疫荧光染色检测肾组织中IgA沉积情况;Western blot检测肾组织中IL-1、Caspase-1及NLRP3的表达。结果阿托伐他汀显著降低血清中Scr、BUN及尿液中红细胞数目、24 h TUP含量;改善IgA的过度沉积和病理损伤,同时阿托伐他汀抑制了IL-1、Caspase-1及NLRP3蛋白的表达(P<0.05)。结论阿托伐他汀改善IgA肾病大鼠肾功能,缓解肾损伤,与抑制NLRP3-(Caspase-1)/IL-1信号通路相关。

Objective To explore the protective effect of atorvastatin on IgA nephropathy rats and to explore the mechanism of its mediating NLRP3 inflammasome. Methods SD rats were randomly divided into control group, model group, atorvastatin low and high dose groups, 10 rats in each group. The rat model of IgA nephropathy was established by oral bovine γ-globulin(BGG) combined with tail vein injection of BGG. After the model was completed, low-and high-dose atorvastatin was given by gavage for 6 weeks. The contents of serum creatinine(Scr), urea nitrogen(BUN), total protein(TP), albumin alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in blood serum were determined;the number of red blood cells in urine and the level of 24 h urinary protein(24 h TUP) were detected;Renal tissue morphological changes were observed by HE staining;IgA deposition in kidney tissue were detected by immunofluorescence staining;IL-1β, Caspase-1 and NLRP3 expression in kidney tissue were detected by Western blot. Results Atorvastatin significantly reduced the number of Scr, BUN in the serum, the number of red blood cells in urine and the 24 h TUP content;Excessive deposition of IgA and pathological damage were improved;In addition, atorvastatin inhibited the expression of IL-1, Caspase-1 and NLRP3 protein(P<0.05). Conclusion Atorvastatin improved renal function and alleviated renal injury in IgA nephropathy rats, and its mechanism may be related to the inhibition of NLRP3-(Caspase-1)/IL-1 signaling pathway.