雷公藤甲素对IgA肾病大鼠的肾保护作用及对NLRP3炎症小体的影响

目的探讨雷公藤甲素对IgA肾病（IgAN）大鼠的肾保护作用及其与NLRP3炎症小体的关系。方法40只SPF级SD雄性大鼠随机分为对照组、模型组和雷公藤甲素低、高剂量组。采用口服牛γ-球蛋白（BGG）8周及尾静脉注射BGG方法建立IgAN大鼠模型。于造模完成后灌胃给予低、高剂量雷公藤甲素治疗8周。观察大鼠血清中肌酐（Scr）、尿素氮（BUN）、总蛋白（TP）、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）及24 h尿蛋白（24 h TUP）水平；血清中肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-17A、γ干扰素（IFN-γ）及IL-4水平；肾组织中IgA沉积情况；肾脏中IL-1β、Caspase-1、IL-18及NLRP3的表达情况。结果与模型组相比，雷公藤甲素组血清Scr、BUN及尿液中24 h TUP含量明显降低（P < 0.05~P < 0.01）；雷公藤甲素能降低血清中TNF-α、IL-17A、IFN-γ和L-4水平（P < 0.05~P < 0.01），减轻IgA的沉积（P < 0.01），抑制IL-1β、Caspase-1、IL-18及NLRP3的表达（P < 0.05~P < 0.01）。结论雷公藤甲素对IgA肾病大鼠肾脏具有保护作用，其作用机制可能是通过抑制NLRP3炎症小体的激活，进而抑制炎症反应。

Effect of Triptolide on renal protection and NLRP3 inflammatome in IgA nephropathy rats

ObjectiveTo investigate the protective effects of triptolide on kidney of IgA nephropathy(IgAN)rats and its relationship with NLRP3 inflammasome.MethodsForty SPF SD male rats were randomly divided into the control group, model group, low-dose triptolide group and high-dose triptolide groups.The IgAN rat model was established by oral bovine γ-globulin(BGG)for 8 weeks and intravenous injection of BGG, and treated with intragastric administration combined with low- and high-dose triptolide for 8 weeks.The levels of creatinine(Scr), urea nitrogen(BUN), total protein(TP), albumin, alanine aminotransferase(ALT), aspartate aminotransferase(AST), 24 h urinary protein(24 h TUP), TNF-α, IL-17A, IFN-γ and IL-4 were detected in four groups.The deposition of IgA and expression levels of IL-1β, Caspase-1, IL-18 and NLRP3 in renal tissue were observed.ResultsCompared with the model group, the levels of serum Scr and BUN, and 24 h TUP significantly decreased in triptolide group(P < 0.05 to P < 0.01).The triptolide could decrease the levels of serum TNF-α, IL-17A, IFN-γ, and IL-4(P < 0.05 to P < 0.01), reduce the deposition of IgA(P < 0.01), and inhibit the expression of IL-1β, Caspase-1, IL-18 and NLRP3(P < 0.05 to P < 0.01).ConclusionsThe protective effects of triptolide on IgA nephropathy may be related to the inhibition of NLRP3 inflammasome for suppressing the renal inflammatory response.