肾衰Ⅱ号方对肾功能衰竭大鼠肠通透性及微炎症的影响

Effects of ShenshuaiⅡDecoction on Intestinal Permeability and Microinflammation in Rats with Renal Failure

目的观察肾衰Ⅱ号方对肾功能衰竭大鼠肠通透性及微炎症的影响,探讨其作用机制。方法采用5/6肾切除法制备大鼠肾功能衰竭模型。40只SD雄性大鼠,随机分为假手术组、模型组、肾衰Ⅱ号方组和阳性对照组。各给药组给予相应药物,假手术组和模型组给予等量生理盐水,共60 d,处死前3.5 h均给予内毒素10 mg/kg灌胃。测试盒分析仪检测血清肌酐(Cr)、尿素氮(BUN)含量,HE染色观察肾脏、肠道病理变化,鳌试剂法检测下腔静脉血浆内毒素含量,ELISA检测相关炎症因子水平,免疫组化和RT-PCR分别检测肠紧密连接蛋白Claudin-1、Occludin蛋白和mRNA的表达。结果与假手术组比较,模型组大鼠肾组织结构紊乱,Cr和BUN、内毒素及炎症因子水平明显升高(P<0.05),Claudin-1、Occludin蛋白和mRNA表达明显降低(P<0.05);与模型组比较,肾衰Ⅱ号方组大鼠肾组织病理变化减轻,肾功能改善,内毒素及炎症因子水平明显降低(P<0.05),Claudin-1、Occludin蛋白表达明显升高(P<0.05),mRNA表达无明显变化。结论肾衰Ⅱ号方可改善5/6肾切除大鼠肾功能水平,调整肠道通透性,减少肠源性内毒素入血,从而改善模型大鼠微炎症状态。

Objective To explore the effects of ShenshuaiⅡDecoction on intestinal permeability and microinflammation in rats with renal failure;To discuss its mechanism.Methods The 5/6 nephrectomy method was used to prepare rat renal failure models.40 male SD rats were randomly divided into control group,sham-operation group,model group,ShenshuaiⅡDecoction group,and positive control group.Each administration group was given corresponding drugs,the sham-operation group and the model group were given the same amount of normal saline for 60 days,and endotoxin 10 mg/kg was given by gavage 3.5 hours before execution.Test kit analyzer was used to detect serum Cr and BUN content.HE staining was used to observe pathological changes of kidney and intestine.Chelol reagent method was used to detect plasma endotoxin content of inferior vena cava.ELISA was used to detect related inflammatory factors.Immunohistochemistry and RT-PCR were used to detect expressions of intestinal tight junction protein Claudin-1,Occludin protein and mRNA.Results Compared with the sham-operation group,the renal tissue structure of the model group was disordered,and the levels of Cr,BUN,endotoxin and inflammatory factors significantly increased (P<0.05), and Claudin-1, Occludin protein and mRNA expressions were significantly reduced(P<0.05). Compared with the model group, the pathological changes of renal tissue were reduced, the renal functionwas improved, the levels of endotoxin and inflammatory factors were reduced, Claudin-1, Occludin proteinexpressions significantly increased in the Shenshuai Ⅱ Decoction group (P<0.05), and no significant change wasfound in mRNA expression. Conclusion Shenshuai Ⅱ Decoction can improve the renal function of 5/6 nephrectomyrats, and adjust intestinal permeability and reducing intestinal endotoxin, in order to improve the microinflammatorystate of model rats.