网络药理学结合转录组测序探讨天舒胶囊对高尿酸血症肾病的干预作用机制OA

Objective:This paper aims to investigate the therapeutic effects of Tianshu Capsule on hyperuricemic nephropathy(HN)rats and to preliminarily explore its mechanisms of action.Methods:A total of 32 rats were randomly and evenly divided into a control group,a model group,a Tianshu Capsule group,and a positive drug(allopurinol)group.The HN rat model was induced and established by intragastric administration of hypoxanthine and intraperitoneal injection of potassium oxonate.The rats of the Tianshu Capsule group and the positive drug(allopurinol)group were intragastrically administered continuously for eight days,while those in the control group and the model group were given an equal amount of sodium carboxymethyl cellulose solution.HE staining was used to detect pathological changes in the kidneys of the rats.The levels of uric acid,creatinine,and urea nitrogen in rats'serum were measured using kits.Network pharmacology was employed to predict the action targets and pathways through which Tianshu Capsule ameliorated HN,and transcriptomics was further used to explore its action targets and pathways.Finally,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was used to verify the mRNA expression of relevant targets in the kidneys of the rats.Results:Compared with those in the control group,the rats in the model group exhibited a reduction in body weight,a significant increase in the kidney index,and significantly elevated levels of uric acid,urea nitrogen,and creatinine in the serum.In contrast to those in the model group,the rats in the Tianshu Capsule group showed recovery of body weight,improved kidney morphology and kidney index,and reduced levels of uric acid,urea nitrogen,and creatinine in the serum after administration.The analysis results of network pharmacology and renal transcriptomics showed that Tianshu Capsule can play a role in ameliorating HN by regulating albumin(ALB),tumor necrosis factor(TNF),signal transducer and activator of transcription 3(STAT3),interleukin-1β(IL-1β),Jun proto-oncogene,and other targets.RT-qPCR results further demonstrate that Tianshu Capsule inhibits the mRNA expression of tumor necrosis factor-α(TNF-α),IL-1β,JUN,extracellular regulated protein kinase(ERK),protein kinase B(Akt),phosphatidylinositol 3-kinase(PI3K),and p38 mitogen-activated protein kinase(p38MAPK)in the renal tissues of HN rats.Conclusion:This study preliminarily confirms that Tianshu Capsule has a therapeutic effect on HN,and its mechanism of action may be related to regulating the expression of targets,including TNF,IL-1β,and JUN.