白虎加桂枝汤加减改善尿酸性肾病大鼠肾小管损伤的机制

目的：观察白虎加桂枝汤对尿酸性肾病（HN）大鼠的治疗效果，并从肾小管损伤角度探讨其作用机制。方法：将60只无特定病原体（SPF）级SD雄性大鼠随机分为正常对照组、模型组、白虎加桂枝汤高剂量组（BHJGZ高组）、白虎加桂枝汤中剂量组（BHJGZ中组）、白虎加桂枝汤低剂量组（BHJGZ低组）、别嘌醇组，每组10只。采用腺嘌呤灌胃联合腹部皮下注射氧嗪酸钾构建大鼠尿酸性肾病模型，连续造模18 d。造模成功后，正常对照组及模型组给予等体积蒸馏水灌胃，其余各组给予对应药物灌胃，连续干预8周。观察大鼠体质量、活动能力、精神状态及毛色，检测大鼠血清尿酸（UA）、血清尿素氮（BUN）、血清肌酐（Scr）、24 h尿蛋白定量（24 h UTP），通过HE染色、过碘酸希夫（PAS）染色和Masson染色，观察高尿酸血症（HUA）大鼠肾脏组织形态学、肾小球系膜增生以及肾间质纤维化情况。结果：与模型组比较，治疗6周后，白虎加桂枝汤各剂量组大鼠体质量增加，活动能力、精神状态及毛色好转（P<0.05）。BHJGZ中组可显著降低大鼠血清Scr水平（P<0.01），BHJGZ中组、BHJGZ高组可明显降低大鼠血清BUN水平（P<0.01）；白虎加桂枝汤各剂量组均可明显降低HUA大鼠血清UA、24 h UTP水平并改善肾组织形态学、肾小球系膜增生及肾间质纤维。结论：白虎加桂枝汤可能通过抑制肾小球系膜基质增生、减少肾小管损伤及肾间质纤维化，延缓HN进展。

Mechanism of Baihu Jiaguizhi Decotion in Attenuating Renal Tubular Injury in Rats with Hyperuricemic Nephropathy

To study the therapeutic effect of Baihu Jiaguizhi Decoction(BHJGZ) on the rats with hyperuricemic nephropathy(HN),and explore the underlying mechanism from renal tubular injury.Methods:Sixty SPF-grade male SD rats were randomly assigned into a normal group,a model group,an allopurinol group,and high-,medium-,and low-dose BHJGZ groups,with 10 rats in each group.The HN rat model was established by gavage of adenine combined with abdominal subcutaneous injection of potassium oxonate for 18 days.After modeling,the normal group and the model group were given an equal volume of distilled water by gavage,and the other groups were given corresponding drugs by gavage for eight weeks.The body weight,activity,mental state,and coat color of the rats were measured and observed.Furthermore,the levels of serum uric acid(UA),serum urea nitrogen(BUN),serum creatinine(Scr),and 24 h urine total protein(24 h-UTP) were measured.Hematoxylin-eosin(HE) staining,periodic acid-Schiff(PAS) staining,and Masson staining were employed to observe the morphology of the kidney tissue,mesangial hyperplasia,and renal interstitial fibrosis in HN rats.Results:Compared with the model group,six weeks of treatment with BHJGZ increased the body weight and activity and improved the mental state and coat color of the rats(P<0.05).Further,the medium-dose BHJGZ reduced the Scr level(P<0.011),and the medium-and high-dose BHJGZ lowered the BUN level(P<0.01).All the doses of BHJGZ significantly reduced the levels of UA and 24 h-UTP,improved renal tissue morphology,and alleviated mesangial hyperplasia and renal interstitial fibersis in HN rats.Conclusion:BHJGZ may inhibit the expansion of glomerular mesangial matrix and reduce renal tubular damage and renal interstitial fibrosis to delay the progression of HN.