高尿酸血症介导肾脏炎症致血压升高机制及别嘌呤醇保护效应OA

Objective:To investigate the mechanism by which hyperuricemia(HUA)elevates blood pressure by inducing renal inflam-matory responses in rats,and to clarify the protective effect of allopurinol.Methods:Thirty SD rats were randomly divided into three groups and subjected to a 60 day exporimental period.(1)Control group(4 females,5 males):Rats were fed a standard pellet diet and given conventional drinking water,with daily distilled water at a dose of 4 mL/(kg·day).(2)HUA group(4 females,5 males):Rats were fed a 0.2%adenine diet and given 0.1 mmol/L uric acid drinking water,and received potassium oxonate via gavage at 250 mg/(kg·day).(3)HUA+allopurinol group(6 fe-males,6 males):Rats received the same interventions as the HUA group from day 1 to day 30,from day 31 to day 60,they were fed a standard pellet diet and conventional drinking water,and received allopurinol at 25 mg/(kg·day).Every 15 days,systolic blood pressure(SBP)and dias-tolic blood pressure(DBP)were measured using the tail-cuff method.Serum levels of uric acid(sUA),creatinine(sCr),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were also measured.One male and one female rat from each group were sacrificed on day 30 and day 45,and all remaining rats were sacrificed on day 60.Kidney tissues were collected and stained with hematoxylin-eosin(HE)for pathological exami-nation.The criteria for successful HUA rat model establishment in this study were:A significant increase in sUA level in HUA rats compared with the control group(P<0.05),accompanied by HUA related changes including abnormal renal function indicators,elevated inflammatory fac-tors,and characteristic pathological damage in kidney tissue.Results:On days 15 and 30,compared with the control group,sUA,sCr,IL-6,TNF-α and blood pressure were significantly increased in the HUA group and HUA+allopurinol group,with typical pathological lesions of HUA in the kidney,indicating successful establishment of the HUA rat model.On days 45 and 60,all indicators kept rising in the HUA group,but were significantly lower in the HUA+allopurinol group than in the HUA group,accompanied by alleviated renal lesion.sUA was positively corre-lated with sCr and SBP.Conclusion:Elevated sUA can lead to renal function impairment and a significant increase in SBP and DBP in rats,and this effect is associated with inflammation.Allopurinol can alleviate these changes.