首页|苦参碱对糖尿病肾病大鼠Th1/Th2细胞平衡的影响

苦参碱对糖尿病肾病大鼠Th1/Th2细胞平衡的影响

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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.
Effects of matrine on the balance of Th1/Th2 cells in diabetes nephropathy rats
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 lipid 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 factor α(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 compared with the control group,the differences of the above indexes were statistically significant(all P<0.05);Matrine group and glycyrrhizic acid group were compared with model group,and the differences were statistically significant(all P<0.05).Conclusion Matrine can alleviate renal inflammation and pathological damage in diabetes nephropathy rats by regulating the balance of Th1/Th2 cells,which may be related to inhibiting the activation of HMGB1/TLR4 signaling pathway.

matrinehigh mobility group box-1/Toll like receptor 4 pathwaydiabetes nephropathyTh1/Th2 cells

张云、杨世霞、马莉

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甘肃省中医院超声医学影像科,甘肃兰州 730050

甘肃省中医院肾内科,甘肃兰州 730050

兰州市第一人民医院心血管二科,甘肃兰州 730050

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

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(1)
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