苦参碱对糖尿病肾病大鼠Th1/Th2细胞平衡的影响  

Effects of matrine on the balance of Th1/Th2 cells in diabetes nephropathy rats

作　　者：张云[1] 杨世霞[2] 马莉 ZHANG Yun;YANG Shi-xia;MA Li(Ultrasound Medical Imaging Department,Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730050,Gansu Province,China;Department of Nephrology,Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730050,Gansu Province,China;Department of Cardiology,Lanzhou First People’s Hospital,Lanzhou 730050,Gansu Province,China)

机构地区：[1]甘肃省中医院超声医学影像科,甘肃兰州730050 [2]甘肃省中医院肾内科,甘肃兰州730050 [3]兰州市第一人民医院心血管二科,甘肃兰州730050

出　　处：《中国临床药理学杂志》2024年第1期72-76,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的基于高迁移率族蛋白1(HMGB1)/Toll样受体4(TLR4)信号通路,探讨苦参碱对糖尿病肾病大鼠的治疗作用及其作用机制。方法用高脂高糖饲养+链脲佐菌素(STZ)溶液注射的方法建立糖尿病肾病模型大鼠。将大鼠分为对照组、模型组、苦参碱组(200 mg·kg^(-1)苦参碱)、HMGB1抑制剂组(10 mg·kg^(-1)甘草酸)。大鼠麻醉后采血,分别检测血糖和血脂水平、肾功能指标、炎性细胞因子水平,观察肾组织病理变化,以流式细胞仪检测大鼠脾组织Th1、Th2细胞水平,以蛋白质印迹法检测HMGB1/TLR4通路相关蛋白表达。结果对照组、模型组、苦参碱组和甘草酸组大鼠的空腹血糖(FBG)水平分别为(5.15±0.61)、(26.24±2.15)、(6.10±0.85)和(5.85±0.74)mmol·L^(-1),总胆固醇(TC)水平分别为(1.56±0.14)、(4.15±0.36)、(1.89±0.15)和(1.82±0.13)mmol·L^(-1),三酰甘油(TG)水平分别为(1.46±0.14)、(11.01±1.00)、(3.04±0.21)和(3.15±0.18)mmol·L^(-1),血清肌酸酐(SCr)水平分别为(23.45±3.26)、(69.78±7.32)、(38.71±5.45)和(41.36±6.02)mmol·L^(-1),尿素氮(BUN)水平分别为(6.27±1.03)、(17.02±1.72)、(9.32±1.04)和(8.35±1.34)μmol·L^(-1),肿瘤坏死因子α(TNF-α)水平分别为(102.35±14.68)、(263.78±18.63)、(134.02±11.47)和(122.35±15.04)pg·mL^(-1),Th1/Th2细胞比值分别为2.71±0.45、14.23±1.01、4.38±0.64和4.03±0.49,HMGB1蛋白相对表达水平分别为0.25±0.03、1.33±0.16、0.64±0.06、0.61±0.08,TLR4蛋白相对表达水平分别为0.33±0.06、1.25±0.18、0.51±0.07和0.47±0.09。上述指标,模型组与对照组比较,差异均有统计学意义(均P<0.05);苦参碱组、甘草酸组与模型组比较,差异均有统计学意义(均P<0.05)。结论苦参碱可以通过调节Th1/Th2细胞平衡,减轻糖尿病肾病大鼠肾组织炎症和病理损伤,这可能与抑制HMGB1/TLR4信号通路激活有关。Objective To explore the therapeutic effect and mechanism of matrine on diabetes nephropathy in rats based on the signal pathway of high mobility group box-1(HMGB1)/Toll like receptor 4(TLR4).Methods The rats with diabetes nephropathy were fed with high fat and high sugar and injected with streptozocin(STZ)solution.The rats were grouped into control group,model group,matrine group(200 mg·kg^(-1)),and HMGB1 inhibitor group(glycyrrhizic acid,10 mg·kg^(-1)),after anesthesia,blood samples were collected to detect blood glucose and lipi d levels,renal function indicators,and inflammatory cytokines levels,respectively.Hematoxylin eosin staining,periodic acid-Schiff staining,and Masson staining were applied to observe the pathological changes of renal tissue;the levels of Th1 and Th2 cells in rat spleen tissue were detected by flow cytometry;Western blot was applied to detect the expression of HMGB1/TLR4 pathway related proteins.Results The levels of fasting blood-glucose(FBG)in control group,model group,matrine group and glycyrrhizic acid group were(5.15±0.61),(26.24±2.15),(6.10±0.85)and(5.85±0.74)mmol·L^(-1),respectively;total cholesterol(TC)levels were(1.56±0.14),(4.15±0.36),(1.89±0.15)and(1.82±0.13)mmol·L^(-1),respectively;triacylglycerol(TG)levels were(1.46±0.14),(11.01±1.00),(3.04±0.21)and(3.15±0.18)mmol·L^(-1),respectively;serum creatinine(SCr)levels were(23.45±3.26),(69.78±7.32),(38.71±5.45)and(41.36±6.02)mmol·L^(-1),respectively;blood urea nitrogen(BUN)levels were(6.27±1.03),(17.02±1.72),(9.32±1.04)and(8.35±1.34)μmol·L^(-1),respectively;tumor necrosis factorα(TNF-α)levels were(102.35±14.68),(263.78±18.63),(134.02±11.47)and(122.35±15.04)pg·mL^(-1),respectively;Th1/Th2 cell ratios were 2.71±0.45,14.23±1.01,4.38±0.64 and 4.03±0.49,respectively;the relative expression levels of HMGB1 protein were 0.25±0.03,1.33±0.16,0.64±0.06,0.61±0.08,respectively;the relative expression levels of TLR4 protein were 0.33±0.06,1.25±0.18,0.51±0.07,0.47±0.09,respectively.Treatment group c

关 键 词：苦参碱 高迁移率族蛋白1/Toll样受体4通路 糖尿病肾病 TH1/TH2细胞 

分 类 号：R28[医药卫生—中药学]