泻浊解毒通络法对糖尿病痛风模型大鼠血清FOXOL、VCAM-1及肾脏病理的影响

Effects of therapy of eliminating turbid,detoxification and dredging collaterals on serum FOXOL and VCAM-1 and renal pathology in model rat of diabetic gout

目的观察具有泻浊解毒通络作用的萆苓祛痛方对糖尿病痛风模型大鼠叉头转录因子(FOXOL)、细胞黏附分子(VCAM-1)及肾脏病理的影响。方法选择健康雄性SD大鼠50只,体质量(200±20) g,除正常组外,其余予高脂饲料喂养并联合小剂量链脲佐菌素35 mg/kg腹腔注射1次,以血糖≥16.7 mmol/L为糖尿病模型。4天后关节腔注射5%尿酸钠溶液1次,诱导痛风模型,模型成功后,萆苓祛痛方组、吲哚美辛组、吡格列酮组继续给药21 d,正常组、模型组予等量0.9%NaCl溶液,21 d后取血测定FOXOL、VCAM-1、Cys C,PG、UA、LDL-C,留取肾脏,观察肾脏病理变化。结果与正常组比较,模型组FOXOL、VCAM-1、Cys-C明显升高(P<0.01);给药后,各药物组的上述指标显著降低(P<0.01);萆苓祛痛方组上述指标优于吡格列酮组(P<0.05,P<0.01)。与正常组比较,模型组血糖、LDL-C明显升高(P<0.01);灌胃后,药物组血糖、LDL-C显著下降(P<0.01)。造模后,模型组血UA、SCr明显升高(P<0.01),用药后各药物组血UA下降(P<0.01);萆苓祛痛方组SCr下降(P<0.05)。相关分析表明,高血糖与高尿酸血症呈相关性(r=0.42,P<0.05)。病理报告示模型组大鼠肾小管间质充血肿胀,空泡样变性,有大量炎细胞浸润。予萆苓祛痛方后病变程度明显减低,肾小管见少量炎细胞浸润。结论具有泻浊解毒通络作用的萆苓祛痛方有良好的降糖、降尿酸、降LDL-C疗效;高血糖与高尿酸具有相关性,可明显下调FOXOL、VCAM-1、Cys-C的高表达,减轻炎症因子对肾脏病理的影响。

Objective To observe the effects of Biling Qutong Prescription,with effects of eliminating turbid,detoxification and dredging collaterals,on FOXOL and VCAM-1 and renal pathology in model rat of diabetic gout.Methods 50 healthy male rats [(200±20)g]were selected.Except the normal group,the rats in the other groups were fed with high-fat diet and treated with low-dose streptozotocin (35mg/kg)by one-time intraperitoneal injection,the blood glucose level equal or greater than 16.7mmol/L was considered as the diabetes model.After 4 days,5% sodium urate solution was injected into the joint cavity to induce the gout model.After successful modeling,the Biling Qutong Prescription group,indomethacin group and pioglitazone group were treated with the correspending drugs for 21 days.The normal group and the model group were treated with 0.9% NaCl solution at equivalent volume.After 21 days,the blood was collected to detect FOXOL,VCAM-1,Cys-C,PG,UA and LDL-C,and the kidneys were collected to observe the pathological changes.Results Compared with the normal group, the FOXOL,VCAM-1 and Cys-C were significantly increased in the model group (P<0.01).After drug treatment,the above indexes in all drug treatment groups were significantly decreased (P<0.01),and the above indexes in the Biling Qutong Prescription group were superior to those in the pioglitazone group (P<0.05, P<0.01).Compared with the normal group,the plasma glucose and LDL-C in the model group were significantly increased (P<0.01).After intragastric administration,the plasma glucose and LDL-C in the drug treatment groups were decreased significantly (P<0.01).After modeling,the blood UA and Scr were significantly increased in the model group (P<0.01),and after drug treatment,the serum uric acid was decreased in all drug treatment groups (P<0.01).The Scr level was decreased in the Biling Qutong Prescription group (P<0.05).Correlation analysis showed that hyperglycemia was associated with hyperuricemia (r =0. 42,P<0.05).Pathological reports showed that there were tubulointerstitial hyperemia and swelling,vacuolar degeneration and lots of inflammatory cells infiltration in the model group.After the treatment with Biling Qutong Prescription,the lesion degree was significantly reduced,and there was a small amount of inflammatory cell infiltration in the renal tubules.Conclusion There is a correlation between hyperglycemia and hyperuricemia.Biling Qutong Prescription,with effects of eliminating turbid,detoxification and dredging collaterals,shows good hypoglycemic effect as well as decreasing uric acid and LDL-C,which can significantly down-regulate the high expressions of FOXOL,VCAM-1and Cys-C,and reduce the influence of inflammatory factors on renal pathology.