健脾益肾降浊方对链脲佐菌素诱导的糖尿病肾病大鼠血清中炎症因子的影响

Effect of Jianpi Yishen Jiangzhuo Formula on inflammatory factors in rats with streptozotocin-induced diabetic kidney disease

目的观察健脾益肾降浊方对糖尿病肾病(DKD)大鼠血清炎症因子的影响,并探讨其治疗DKD的可能机制。方法共选取健康雄性SD大鼠60只,10只作为正常组,其余50只予高糖高脂饮食,并腹腔注射链脲佐菌素建立DKD模型。将造模成功的大鼠随机分为模型组(n=10)、缬沙坦组(n=10)、健脾益肾降浊方低剂量组(n=9)、健脾益肾降浊方中剂量组(n=9)、健脾益肾降浊方高剂量组(n=9)。健脾益肾降浊方低、中、高剂量组分别予健脾益肾降浊方1.032 g/kg、2.064 g/kg、4.128 g/kg灌胃,缬沙坦组予缬沙坦0.131 g/kg灌胃,正常组及模型组予等容积0.9%氯化钠注射液灌胃。连续灌胃12周后检测各组大鼠空腹血糖(FPG)、餐后2 h血糖(2 hPG)、血肌酐(SCr)、白细胞介素6(IL-6)、IL-8、肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)、24 h尿微量白蛋白水平。苏木素-伊红染色(HE)观察各组大鼠肾组织病理变化。结果与正常组比较,模型组大鼠FPG、2 hPG水平均升高(P<0.05);与模型组、缬沙坦组、健脾益肾降浊方低剂量组比较,健脾益肾降浊方中、高剂量组大鼠FPG、2 hPG水平均降低(P<0.05)。各组大鼠SCr水平比较差异无统计学意义(P>0.05)。与正常组比较,模型组大鼠24 h尿微量白蛋白水平升高(P<0.05);与模型组比较,缬沙坦组及健脾益肾降浊方中、高剂量组大鼠24 h尿微量白蛋白水平均降低(P<0.05),健脾益肾降浊方低剂量组无明显改善(P>0.05);与健脾益肾降浊方低剂量组比较,健脾益肾降浊方中、高剂量组大鼠24 h尿微量白蛋白水平均降低(P<0.05);与健脾益肾降浊方中剂量组比较,健脾益肾降浊方高剂量组大鼠24 h尿微量白蛋白降低(P<0.05)。与正常组比较,模型组大鼠IL-6、IL-8、TNF-α、CRP水平均升高(P<0.05);与模型组比较,缬沙坦组及健脾益肾降浊方中、高剂量组大鼠IL-6、IL-8、TNF-α、CRP水平及低剂量组IL-8、CRP水平均降低(P<0.05);与缬沙坦组比较,健脾益肾降浊方中剂量组IL-8、CRP水平及高剂量组IL-6、IL-8、TNF-α、CRP水平均降低(P<0.05);与健脾益肾降浊方低剂量组比较,健脾益肾降浊方中剂量组大鼠IL-6、IL-8、TNF-α水平及高剂量组大鼠IL-6、IL-8、TNF-α、CRP水平均降低(P<0.05);与健脾益肾降浊方中剂量组比较,健脾益肾降浊方高剂量组大鼠IL-6、IL-8、TNF-α、CRP水平均降低(P<0.05)。结论健脾益肾降浊降浊方可以降低糖尿病肾病大鼠的血糖、24 h尿微量白蛋白及炎症因子水平,改善肾脏病理的损伤。

Objective To observe the effect of Jianpi Yishen Jiangzhuo Formula(JPYSJZF)on serum inflammatory factors in rats with diabetic kidney disease(DKD),and explore its mechanism.Methods Totally 60 healthy male SD rats were selected,except for 10(normal group),and 50 were given high-glucose-high-fat diet and intraperitoneal injection of streptozotocin to establish DKD model.Successful rat models were randomly assigned to receive enema1.032 g·kg^(-1),2.064 g·kg^(-1),4.128 g·kg^(-1) of JPYSJZF(low-,medium-and high-dose JPYSJZF groups,with 9 in each group)or 0.131 g·kg^(-1) of valsartan(valsartan group,n=10)or 0.9%Sodium Chloride Injection(model group,n=10).The normal group was given equal volume 0.9%Sodium Chloride Injection by gavage.The treatment was porformed for 12 weeks.Fasting plasma glucose(FPG),2-h plasma glucose(2 h-PG),serum creatinine(Cr),interleukin-6(IL-6),IL-8 and tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),24-h urinary microalbumin were included as comparators.Hematoxylin-eosin(HE)staining was used to observe the renal biopsy pathology.Results Compared with normal group,FPG and 2 hPG in model group were increased(P<0.05),which in medium-and high-dose JPYSJZF groups were lower than those in model group,valsartan group,low-dose JPYSJZF group(P<0.05).The difference was not statistically significant in Cr among groups(P>0.05).Compared with normal group,the 24-h 24 h urinary microalbumin excretion(UAE)in model group was increased(P<0.05),which in valsartan group,medium-and high-dose JPYSJZF groups was decreased(P<0.05),but which was comparable between low-JPYSJZF group and model group(P>0.05).The difference was statistically significant in 24-h UAE between the high-dose JPYSJZF group and medium-dose JPYSJZF,and medium-dose JPYSJZF group and low-dose JPYSJZF group lower than(all P<0.05).Compared with normal group,IL-6,IL-8,TNF-αand CRP in model group were increased(P<0.05);which were lower in valsartan group and medium-and high-dose JPYSJZF groups,but only IL-8,CRP in low-dose JPYSJZF group were detected(all P<0.05).Compared with valsartan group,IL-8 and CRP in medium-dose JPYSJZF group and IL-6,IL-8,TNF-αand CRP in high-dose JPYSJZF group were decreased(P<0.05).Compared with the low-dose JPYSJZF group,IL-6,IL-8,TNF-αin medium-dose JPYSJZF group and IL-6,IL-8,TNF-α,CRP in JPYSJZF group were decreased(P<0.05).IL-6,IL-8,TNF-α,CRP in high-dose JPYSJZF group were decreased than those in medium-dose JPYSJZF group(P<0.05).Conclusion For DKD rats,JPYSJZF can reduce blood sugar,24-h UAE and inflammatory factors,and improve renal pathological damage.