Mechanism of Yishen Qingli Huoxue Formula on Aristolochic Acid Ⅰ-Induced Renal Injury Based on Transcriptomics
Objective:Yishen Qingli Huoxue(YQH)formula is created by Chinese medical master Zou Yanqin,based on his belief that"kidney deficiency leading to the dampness stagnation"is the basic pathogenesis.This study aims to explore the therapeutic mechanism and target of YQH formula through animal experiments and transcriptomic sequencing analysis.Methods:Forty-eight male C57BL/6 mice were randomly divided into normal control group,model group,and YQH low-dose and high-dose groups,with 12 mice in each group.Except for the normal control group,mice in the other groups were intraperitoneally injected with 0.1 mL of aristolochic acid Ⅰ(AAⅠ)[5 mg/kg·3d,AAⅠ dissolved in 0.5%sodium carboxymethyl cellulose]to create the model.YQH low-dose group was gavaged 11 g/kg·d lyophilized YQH formula powder,YQH high-dose group was gavaged 22 g/kg·d lyophilized YQH formula powder,and the normal control group and the model group were given 0.3 mL PBS solution containing 0.5%sodium carboxymethyl cellulose by gavage,for 30 days.After the experiment,the bloody urine and bilateral kidneys of the mice were collected,the levels of serum creatinine,uric acid and urinary protein were measured,and renal tissue was stained by HE and Masson.Four kidneys were taken from the normal control group,model group,and YQH low-dose group respectively,and the mechanisms and targets of YQH formula were analyzed by transcriptomic analysis.Finally,the core targets were validated by qPCR.Results:YQH formulae could reduce the levels of uric acid,urinary protein and blood creatinine in AAⅠ mice.Pathological staining results showed that there were a large number of inflammatory cell infiltration,that the collagen deposition increased in AAⅠ induced mice,and that the condition could be significantly improved by YQH formula.Transcriptomic analysis showed that there were 368 different genes in the model group and the YQH low-dose group,and functional enrichment analysis showed that this was closely related to inflammation.KEGG enrichment analysis showed that it was mainly involved in PPAR,glutathone metabolism,fatty acid degradation,IL-17 and other signaling pathways,and that 37 key genes included Ppara,Fabp1,Apoa2,Acox1 and Hspa5.The first 8 core genes verified by qPCR showed statistically significant differences among all groups.Conclusion:Yishen Qingli Huoxue formula can protect renal function,reduce inflammation and collagen deposition in kidney tissue,and transcriptomic analysis showed that it was closely related to fatty acid metabolism,iron death and IL-17 signaling pathway.
万方数据
维普
