Research On The Intervention Mechanism Of Yishenhuoxue Prescription To Renal Fibrosis Through The Signal Regulation By MiRNA To VEGF-Notch

Objective:To observe the influence of Yishenhuoxue Prescription on the function and pathological changes and the related cytokines factors of mi R-126,VEGFA,VEGFR-2,Notch1 in kidney of UUO rat,and to discuss the mechanism about mi R-126 controlling the signal channel of VEGF-Notch and the effect and intervention mechanism of Yishenhuoxue Prescription acting on renal fibrosis.Methods:90 rats were randomly divided into the sham operation group,the Chinese medicine group,the western medicine group and the model group.The Chinese medicine group(with high,medium and low doses),the western medicine group and the model group were established the model of renal fibrosis by ligaturing the left kidney ureter of rats,while the sham operation group was select the left kidney only,without ureter ligation.And than,four groups of rats were given gastric infusion after the operation.The sham operation group and the model group were given saline gavage daily,while the Chinese traditional medicine group was gavaged with Yishenhuoxue Prescription and the western medicine group with losartan.Next,left renal tissues of rats were extracted after 7days,14 days and 21 days postoperatively.The renal pathological changes were observed through biochemical detection of BUN,Scr,HE and Masson and evaluated by the pathological scoring criteria.Furthermore,the expression was detected by RT-q PCR on mi RNA126,VEGFA,VEGFR-2,Notch1 m RNA of renal tissues.Results:(1)Biochemical result showed that compared with the UUO model group,the sham operated group and all the treatment groups' Scr,BUN level declined obviously,but there were no statistically significant differences between them(P >0.05);(2)Pathology results::we used the software system of statistical analysis to deal with renal fibrosis grading,the results showed that:compared with the sham operation,the renal fibrosis level of UUO model group had significantly increased all the time points(P<0.01);compared with the UUO model group,the renal fibrosis level of Chinese medicine group(with medium and high doses)had significantly declined all the time points(P<0.01),the renal fibrosis level of Chinese medicine group(with low dose)and western group had no statistically significant all the time points(P> 0.05);compared with the losartan group,the renal fibrosis level of Chinese medicine group(with medium and high doses)had declined all the time points,but there were no statistically significant differences between them(P>0.05),the renal fibrosis level of Chinese medicine group(with low dose)had increased(P < 0.05);(3)The RT-q PCR results showed that:compared with the sham operation,the expression of mi R-126,VEGFA,VEGFR-2 and Notch1 in the UUO model group had increased all the time points(P < 0.05);compared with the UUO model group,the expression of mi R-126,VEGFA,VEGFR-2 and Notch1 in the Chinese medicine group(with medium and high doses)and the losartan group had significantly increased all the time points(P < 0.01 ? P < 0.05);the expression of mi R-126 and VEGFA in the 21 days of Chinese medicine group(with low doses)had declined,but there were no statistically significant differences between them(P >0.05),the expression of VEGFR-2 and Notch1 in the Chinese medicine group(with low doses)all the time points had no statistically significant differences between them(P>0.05);compared with the losartan group,the expression of mi R-126,VEGFA,VEGFR-2 and Notch1 in the Chinese medicine group(with medium and high doses)had increased all the time points,but there were no statistically significant differences between them(P>0.05),the expression of mi R-126,VEGFA,VEGFR-2 and Notch1 in the Chinese medicine group(with low doses)had declined all the time(P <0.05).Conclusion: YiShen Huo Xue Prescription may use up-regulation the signaling pathways of mi R-126/VEGF-Notch to mediate renal microvascular newly born,eventually to improve renal microvascular damage and delay the development of renal fibrosis progression.