摘要
目的:旨在探究三黄益肾胶囊治疗糖尿病肾病(DN)可能的炎症反应机制.方法:按照随机数字表法将60只大鼠分为正常组、模型组、厄贝沙坦组及三黄益肾低、中、高剂量组,每组10只.除正常组外,其余各组大鼠用高糖高脂饲料联合链脲佐菌素(STZ)注射建立DN模型.正常组和模型组给予生理盐水2 mL灌胃;厄贝沙坦组给予厄贝沙坦11.51 mg/kg灌胃;三黄益肾低、中、高剂量组分别给予三黄益肾胶囊0.41、0.81、1.62 g/kg灌胃.各组大鼠均1次/d,连续给药4周.比较各组大鼠空腹血糖(FBG)、体质量、24 h尿白蛋白、肾功能指标、肾组织病理学变化、肾组织抗氧化相关指标(SOD、GSH-Px活性及MDA水平)、肾组织炎症介质[白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)]、肾组织诱导型一氧化氮合酶(iNOS)、肾组织CD68、CC趋化因子受体2(CCR2)表达、肾组织CC趋化因子配体2(CCL2)、NF-κB P65、p-NF-κB P65、IκB、p-IκB表达.结果:与模型组比较,各三黄益肾胶囊组大鼠体质量高,FBG、血清肌酐(Cr)、尿素氮(BUN)及24 h尿蛋白水平低,肾脏组织病理变化减轻,三肾组织中SOD、GSH-Px活性高,MDA水平低,IL-6、IL-1β、TNF-α水平低,肾组织中iNOS水平低,肾组织CCR2与CD68共定位水平低,CCL2、p-NF-κB P65、p-IκB蛋白表达低.结论:三黄益肾胶囊治疗DN的机制可能与抑制肾组织中NF-κB信号通路激活,减轻肾脏氧化应激及炎症反应有关.
Abstract
Objective:To explore the potential inflammatory response mechanism of the Sanhuang Yishen Capsules in the treatment of diabetic nephropathy(DN).Methods:Sixty rats were divided into the normal group,model group,irbesartan group,and low,medium,and high dose Sanhuang Yishen Capsules groups according to the random number table method,with 10 rats in each group.Except for the nor-mal group,the other groups were fed a high-sugar and high-fat diet combined with streptozotocin(STZ)injection to establish a DN mod-el.The normal and model groups were given 2 mL of normal saline via gavage;the irbesartan group was given 11.51 mg/kg of irbesartan via gavage;and the low,medium,and high dose Sanhuang Yishen Capsules groups were given 0.41,0.81,and 1.62 g/kg of Sanhuang Yishen Capsules via gavage,respectively.All groups received the treatments once daily for 4 consecutive weeks.The following indexes a-mong the groups were compared among the groups:fasting blood glucose(FBG),body weight,24-hour urine albumin,renal function indi-cators,renal histopathological changes,renal tissue oxidative stress-related indicators(SOD,GSH-Px activity,and MDA levels).The ex-pression levels of renal tissue inflammatory mediators[Interleukin-6(IL-6),interleukin-1β(IL-1 β),tumor necrosis factor-a(TNF-a)],renal tissue inducible nitric oxide synthase(iNOS),renal tissue CD68,CC chemokine receptor 2(CCR2),and renal tissue CC chemokine ligand 2(CCL2),NF-κB P65,p-NF-κB P65,IκB kinase(IKB),p-IκB were also compared among the groups.Results:Compared with the model group,rats in the Sanhuang Yishen Capsules groups had higher body weight and lower levels of FBG,serum creatinine(Cr),blood urea nitrogen(BUN),and 24-hour urine protein.The renal histopathological changes were alleviated,and the activities of SOD and GSH-Px in renal tissues were higher,while the MDA levels were lower.Levels of IL-6,IL-1 β,TNF-a,and iNOS in renal tissues were lower.The co-localization level of CCR2 and CD68 in renal tissues was lower,as well as the expressions of CCL2,p-NF-KB P65,and p-IκB proteins.Conclusion:The mechanism of Sanhuang Yishen Capsules in the treatment of DN may be related to the inhibition of NF-κB signaling pathway activation in renal tissues,and the reduction of renal oxidative stress and inflammatory response.
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