补阳还五汤对糖尿病肾病大鼠肾脏氧化应激及NF-κB通路的影响

Effects of Buyang Huanwu Decoction on renal oxidative stress and NF-κB pathway in diabetic nephropathy rats

目的观察补阳还五汤对DN模型大鼠肾脏氧化应激及NF-κB通路的影响。方法将60只SD大鼠按随机数字表法分为正常组,模型组,补阳还五汤低、中、高剂量组,二甲双胍组,每组10只。正常组给予普通饲料,其余各组给予高脂高糖饲料喂养6周后,腹腔注射35 mg/kg的STZ建立DN模型。造模成功后,补阳还五汤低、中、高剂量组分别灌胃补阳还五汤7.42、14.84、29.68 g/kg,二甲双胍组灌胃二甲双胍水溶液0.2 g/kg,连续给药6周。测量各组大鼠体重,检测大鼠24 h尿蛋白定量、血清SCr、BUN及肾组织GSH-Px、SOD、CAT、MDA水平;采用Westerrn Blot法检测大鼠肾组织NF-κBp65、p-NF-κBp65、TNF-α、IL-6蛋白表达水平。结果与模型组比较,补阳还五汤低、中、高剂量组大鼠体重增高(P<0.01),血清24 h尿蛋白定量、SCr、BUN水平降低(P<0.05或P<0.01);肾组织GSH-Px、SOD、CAT活性升高(P<0.05或P<0.01),MDA水平降低(P<0.05或P<0.01);肾组织中NF-κBp65[(0.53±0.07)、(0.46±0.09)、(0.42±0.10)比(0.67±0.13)]、p-NF-κBp65[(0.51±0.12)、(0.43±0.06)、(0.34±0.17)比(0.59±0.07)]、TNF-α[(1.21±0.08)、(1.17±0.04)、(1.05±0.22)比(1.43±0.21)]、IL-6[(0.92±0.04)、(0.89±0.25)、(0.73±0.09)比(1.06±0.08)]蛋白表达降低(P<0.05或P<0.01)。结论补阳还五汤可改善DN模型大鼠肾组织氧化应激状态和炎症损伤,其机制可能与抑制NF-κB信号通路有关。

Objective To observe the effect of Buyang Huanwu Decoction on renal oxidative stress and NF-κB pathway in diabetic nephropathy rats.Methods Sixty SD rats were randomly divided into normal group,model group,low,medium,and high dose of Buyang Huanwu Decoction groups and metformin group,with 10 rats in each group.The normal group was given ordinary diet every day,and the other groups were given high-fat and high-sugar diet for 6 weeks,then intraperitoneally injected 35 mg/kg STZ to establish diabetic nephropathy model.After successful modeling,the rats were orally injected with 7.42,14.84 and 29.68 g/kg of low-dose,medium-dose and high-dose Buyang Huanwu Decoction and metformin group was orally given metformin solution 0.2 g/kg.After 6 weeks of feeding,the body weight,24h urinary protein,serum creatinine and urea nitrogen were detected.The levels of GSH-Px,SOD,CAT and MDA in rats'kidney of each group were detected.The protein expression levels of NF-κBp65,p-NF-κBp65,TNF-αand IL-6 in rats'kidney in each group were detected by Western Blot.Results Compared with model group,the body weight of the low,medium and high dose of Buyang Huanwu Decoction groups were increased(P<0.01),the content of 24 h urinary protein,serum creatinine and urea nitrogen were decreased(P<0.05 or P<0.01),the content of GSH-Px,SOD,CAT were significantly increased(P<0.05 or P<0.01),the content of MDA was significantly decreased(P<0.05 or P<0.01),the expression of NF-κB p65(0.53±0.07,0.46±0.09,0.42±0.10 vs.0.67±0.13),p-NF-κB p65(0.51±0.12,0.43±0.06,0.34±0.17 vs.0.59±0.07),TNF-α(1.21±0.08,1.17±0.04,1.05±0.22 vs.1.43±0.21),IL-6(0.92±0.04,0.89±0.25,0.73±0.09 vs.1.06±0.08)were significantly decreased(P<0.05 or P<0.01).Conclusion Buyang Huanwu Decoction can improve oxidative stress state and inflammatory damage in renal tissue.The mechanism may be related to the inhibition of NF-κB signaling pathway.