Study on Mechanism of Shenyan Zhixue Pills(肾炎止血丸)on IgA Nephropathy Rats Based on lncRNA TUG1 Mediating miR-320 Regulation of PTEN/Cosmc Signaling Pathway
Objective:To observe the therapeutic effects of Shenyan Zhixue Pills on rats with IgA ne-phropathy and explore its impact on the lncRNA TUG1-mediated miR-320 regulation of the PTEN/Cosmc pathway.Methods:IgA nephropathy(IgAN)rat models were constructed using a combination of bovine serum albumin,carbon tetrachloride,and lipopolysaccharide.32 rats were randomized into four groups:normal con-trol,model,Losartan potassium[20 mg/(kg·d)],and Shenyan Zhixue Pills[3.6 g/(kg·d)],with 8 rats in each group and continuous administration for 6 weeks.Blood,intestinal mucosa and renal tissue specimens were retained,and serum PTEN,Cosmc,and Gd-IgA1 levels were measured by ELISA;The expressions of lncRNA TUG1,miR-320,PTEN,and Cosmc mRNA and protein in intestinal mucosal tissue and kidney tissue were de-termined by Real-time PCR and Western blot.Results:① Serum PTEN,Cosmc,Gd-IgA1:Compared with the model group,PTEN and Cosmc were elevated significantly(all P<0.01)and Gd-IgA1 was reduced signi-ficantly(P<0.01)in each administration group,and compared with the group of Losartan potassium tablets,PTEN and Cosmc were elevated and Gd-IgA1 was reduced significantly in the Shenyan Zhixue Pills group(all P<0.01).② RT-PCR method for the detection of intestinal mucosal tissue and renal tissue lncRNA TUG1,miR-320,PTEN,Cosmc mRNA expression:Compared with the model group,the intestinal mucosal tissue and renal tissue of the Losartan potassium tablet group TUG1 was elevated significantly(both P<0.01),miR-320 was reduced significantly(P<0.01),and compared with the Losartan potassium tablet group,the Shenyan Zhixue Pills intestinal TUG1 and PTEN of mucosal and renal tissues were elevated significantly,Cosmc of intesti-nal tissues was elevated significantly(both P<0.01),and miR-320 of renal tissues was reduced significantly(P<0.01).③ Western blot detection of PTEN and Cosmc protein expression in intestinal mucosal tissue and kidney tissue:Compared with the model group,PTEN protein expression in intestinal mucosal tissue of each ad-ministered group was elevated(P<0.05),and Cosmc expression in Shenyan Zhixue Pills group was elevated significantly(P<0.05);compared with the group of Losartan potassium tablets,there was a significant diffe-rence in the elevation of PTEN in Shenyan Zhixue Pills(P<0.05),and there was no significant difference in the elevation of Cosmc expression(P>0.05).There was a highly significant difference(P<0.01)in the ele-vated Cosmc expression in renal tissues of each administration group;compared with the Losartan potassium tab-let group,there was a significant difference(P<0.05)in the elevated PTEN of Shenyan Zhixue Pills,and a highly significant difference(P<0.01)in the elevated Cosmc expression.Conclusion:Shenyan Zhixue Pills a-meliorates renal injury in IgAN rats.Its mechanism may be related to the involvement in the regulation of PTEN/Cosmc pathway mediated by lncRNA TUG1 via miR-320.