Mesaconine Inhibits Apoptosis through the BAX/BCL-2/Caspase 3 Signaling Pathway to Improve Renal Fibrosis in Rats with Chronic Renal Failure
Objective:To investigate whether mesaconine inhibits apoptosis through the Bax/Bcl-2/caspase 3 signaling pathway to improve renal fi-brosis in rats with chronic renal failure(CRF).Methods:Male SD rats were used to establish CRF model by 5/6 nephrectomy,and the rats were randomly divided into model group,mesaconine 2 mg/kg group,mesaconine 5 mg/kg group and enalapril 2 mg/kg group.Other rats were taken as blank group and sham operation group.One week after operation,the rats were given drugs by gavage for 8 weeks.After the last drug administration,24-h urine was collected to detect urine volume and protein content.Blood and renal tissue were collected to determine the level of serum renal injury markers,including creatinine(CREA)and blood urea nitrogen(BUN),as well as the level of renal fibrosis mark-ers,including transforming growth factor-β1(TGF-β1)and α-smooth muscle actin(α-SMA).HE staining and Masson staining were per-formed to observe the pathological changes and renal fibrosis.TUNEL staining was conducted to observe the apoptosis rate of renal cells.Western blot method was used to detect the expressions of apoptosis-related proteins,such as Bax,Bcl-2 and cleaved-caspase 3.Results:Compared with the blank group or sham operation group,the rats in the model group showed significantly lower urine volume,as well as signifi-cantly increased urine protein,serum contents of CREA,BUN,TGF-β1 and α-SMA,pathological score of kidney histological damage,fibrosis degree and apoptosis rate of renal cells.The protein expressions of Bax and cleaved-caspase 3 were significantly upregulated,while the expres-sion level of Bcl-2 was significantly downregulated(P＜0.05 or P＜0.01).Compared with the model group,the rats in the mesaconine 5 mg/kg group exhibited remarkably elevated urine volume.The urinary protein level,serum contents of CREA,BUN,TGF-β1 and α-SMA,pathological score of renal tissue injury,degree of fibrosis,and apoptosis rate of renal cells were significantly decreased in all treatment groups.The expressions of Bax and cleaved-caspase 3 protein in renal tissue were significantly downregulated,while the protein expression of Bcl-2 was significantly upregulated(P＜0.05 or P＜0.01).Conclusion:Mesaconine effectively improves renal function in 5/6 nephrectomy-induced CRF rat model.Its renal protective effect is potentially associated with the modulation of the Bax/Bcl-2/caspase 3 signaling pathway to inhibit apoptosis,thereby reducing renal fibrosis in the CRF rat model.
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