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目的观察14-脱羟-11,12-二脱氢穿心莲内酯对1型糖尿病急性心肌缺血大鼠心肌组织的保护作用。方法选取50只SD大鼠分为正常组和实验组,正常组10只大鼠,实验组40只大鼠均一次性腹腔注射1%链脲佐菌素(STZ)55 mg/kg,制造1型糖尿病动物模型,后选取造模成功的30只大鼠随机分为模型组、药物低剂量组、药物高剂量组,每组10只。药物低、高剂量组分别给予14-脱羟-11,12-二脱氢穿心莲内酯100 mg·kg~(-1)·d~(-1)、200 mg·kg~(-1)·d~(-1),正常组和模型组分别腹腔注射等体积的0.9%氯化钠注射液,连续给药14 d。给药结束后24h,除正常组外,各组大鼠均皮下注射异丙肾上腺素(ISO)5 mg/kg,记录注射异丙肾上腺素后大鼠的Ⅱ导心电图,根据ST段(J点)的偏移判断心肌缺血的程度。断尾取血,测空腹血糖;腹主动脉取血,检测生化指标,苏木精-伊红(HE)染色观察大鼠心肌组织的形态变化,蛋白质印迹法检测心肌核因子(NF)-_κBp65的表达,免疫组织化学检测肿瘤坏死因子(TNF)-α的表达量。结果 14-脱羟-11,12-二脱氢穿心莲内酯100 mg·kg~(-1)·d~(-1)、200 mg·kg~(-1)·d~(-1)组均能降低1型糖尿病大鼠急性心肌缺血时的空腹血糖,可降低肌酸激酶(CK)、乳酸脱氢酶(LDH1)(P<0.05),200 mg·kg~(-1)·d~(-1)组能显著改善糖尿病急性心肌缺血大鼠心电图ST段的偏移程度(P<0.01),100 mg·kg~(-1)·d~(-1)组对ST段的偏移改善不明显(P>0.05)。100 mg·kg~(-1)·d~(-1)组、200 mg·kg~(-1)·d~(-1)组均能改善大鼠的心肌组织病理改变,显著减少TNF-α的表达(P<0.05)和NF-_κBp65的表达(P<0.05)。结论 14-脱羟-11,12-二脱氢穿心莲内酯能降低糖尿病急性心肌缺血大鼠心肌组织中NF-_κBp65、TNF-α的表达,改善心肌组织的损伤。
Objective To observe the protective effects of andrographolide, 14-dehydro-11,12-didehydro-andrographolide, on myocardial tissue in type 1 diabetes mellitus rats with acute myocardial ischemia. Methods Fifty SD rats were divided into normal group and experimental group, normal group was 10 rats, and 40 rats in experimental group were intraperitoneally injected with 1% streptozotocin (STZ) 55 mg/kg. In the animal model of type 2 diabetes, the 30 rats successfully selected for modeling were randomly divided into model group, low dose group, and high dose group, with 10 in each group. 14-dehydroxy-11,12-didehydroandrographolide 100 mg·kg -1 ·d -1 and 200 mg·kg -1 were given to low and high dose groups, respectively d ~ (-1), normal group and model group were injected intraperitoneally with equal volume of 0.9% sodium chloride injection for 14 days. 24 h after the end of the administration, except for the normal group, rats in each group were injected subcutaneously with isoproterenol (ISO) 5 mg/kg, and the II-lead electrocardiogram of rats after the injection of isoproterenol was recorded, according to the ST segment (point J). The degree of deviation was determined by the degree of myocardial ischemia. After taking blood from the tail off, fasting blood glucose was measured; blood was taken from the abdominal aorta, biochemical parameters were measured, hematoxylin-eosin (HE) staining was used to observe the morphological changes of myocardial tissue in rats, and myocardial nuclear factor (NF)-_κBp65 was detected by Western blotting. The expression of tumor necrosis factor (TNF)-alpha was detected by immunohistochemistry. Results 14-dehydroxy-11,12-didehydroandrographolide 100 mg·kg -1 ·d -1,200 mg·kg -1 ·d -1 All can reduce the fasting blood glucose in type 1 diabetes mellitus rats with acute myocardial ischemia, can reduce creatine kinase (CK), lactate dehydrogenase (LDH1) (P <0.05), 200 mg · kg ~ (-1) · d The ~(-1) group could significantly improve the ST-segment deviation of electrocardiogram in diabetic rats with acute myocardial ischemia (P<0.01), and the 100 mg·kg -1 ·d -(1) group had an effect on ST segment. The shift was not significantly improved (P>0.05). 100 mg·kg -1 ·d -1 group and 200 mg·kg -1 ·d -1 group could improve the pathological changes of myocardium and significantly reduce TNF- Expression of α (P<0.05) and expression of NF-κBp65 (P<0.05). Conclusion 14-dehydro-11,12-didehydroandrographolide can reduce the expression of NF-κBp65 and TNF-α in the myocardium of diabetic rats with acute myocardial ischemia and improve the myocardial tissue damage.