Discussion on the mechanism of Buyang Huanwu Decoction and Didang Decoction improving renal injury in rats with uric acid nephropathy based on autophagy pathway
Objective:To investigate the therapeutic effect and mechanism of Buyang Huanwu Decoction and Didang Decoction on renal fibrosis in rats with uric acid nephropathy(UAN).Methods:A total of 48 male SPF SD rats were randomly divided into blank control group,model group,allopurinol group,Buyang Huanwu Decoction and Didang Decoction high,medium and low dose groups,with 8 rats in each group.The UAN model was established by intragastric administration of Adenine(100 mg/kg)combined with Potassium Oxonate(300 mg/kg).At the same time,Allopurinol(5 mg/kg)and Buyang Huanwu Decoction and Didang Decoction(3.46,1.73,0.87 g/kg)were given by intragastric administration for 21 days.The body weight,kidney weight and kidney index were observed.The levels of serum uric acid(SUA),serum creatinine(Scr),blood urea nitrogen(BUN)and 24h urinary microalbumin(24h mAlb)were detected.HE staining was used to observe the pathological changes of renal tissue.Masson staining was used to observe the proportion of collagen positive area in renal tissue.Immunohistochemical staining was used to detect the expressions of CD68 and α-SMA in renal tissue.The mRNA expressions of autophagy marker proteins LC3-Ⅱ,Beclin-1 and P62 in renal tissue were detected by real-time PCR.The ratio of autophagy marker protein LC3-Ⅱ/LC3-Ⅰ and the expression of Beclin-1 and P62 proteins were detected by Western Blot.Results:Compared with the blank control group,the body weight of rats in the model group significantly decreased(P＜0.01),significantly increased renal index(P＜0.01),serum SUA,Scr,BUN and urine 24 h mAlb content significantly increased(P＜0.01),renal collagen volume fraction(CVF)significantly increased(P＜0.01),and the positive expression areas of CD68 and α-SMA in renal tissues were significantly increased(P＜0.01).The mRNA expression of autophagy marker protein LC3-Ⅱ and the ratio of LC3-Ⅱ/LC3-Ⅰ in renal tissue were significantly increased(P＜0.01),and the mRNA and protein expression of Beclin-1 were significantly increased(P＜0.01),and P62 expression was significantly decreased(P＜0.01),accompanied by sodium urate crystal deposition and renal tissue damage and other pathological changes.Compared with the model group,the body weight of the rats in the high and middle dose of Chinese medicine groups significantly increased(P＜0.01).The renal index of allopurinol group and Buyang Huanwu Decoction and Didang Decoction high and medium dose groups significantly decreased(P＜0.01).The levels of serum SUA,Scr and BUN in each drug intervention group were significantly decreased(P＜0.05,P＜0.01),while the contents of 24h mAlb in urine significantly decreased in the Buyang Huanwu Decoction and Didang Decoction high and middle dose groups(P＜0.05,P＜0.01).The pathological changes of renal tissue in each drug intervention group were improved to varying degrees,and the middle dose group was closer to the blank control group.The CVF of the allopurinol group and the Buyang Huanwu Decoction and Didang Decoction high and middle dose groups significantly decreased(P＜0.01).The positive expression areas of CD68 and α-SMA,the mRNA expression of autophagy marker protein LC3-Ⅱ and the ratio of LC3-Ⅱ/LC3-Ⅰ in renal tissues were significantly decreased(P＜0.01),and the mRNA and protein expressions of Beclin-1 were significantly decreased(P＜0.01),and P62 gene and protein expression were significantly increased(P＜0.01).Conclusion:Buyang Huanwu Decoction and Didang Decoction have anti-inflammatory and anti-fibrosis effects on the kidney of UAN rats,which may be related to the abnormal expression of LC3-Ⅱ,Beclin-1 and P62.
Buyang Huanwu Decoction and Didang DecoctionUric acid nephropathy(UAN)Kidney injuryAutophagy pathwayMechanism
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