糖心乐对糖尿病心肌病大鼠心肌酶及心肌转化生长因子β_1的影响
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摘要
目的探讨糖心乐(TXL)对糖尿病心肌病大鼠心肌酶、心肌转化生长因子β1(TGF-β1)表达的影响。方法SD大鼠腹腔注射链脲佐菌素建立糖尿病模型,8周后形成糖尿病心肌病模型,随机分为模型对照组、达美康对照组、TXT大、小剂量组,各组大鼠均为12只,另设正常SD大鼠10只作为正常对照组。达美康对照组、TXL大、小剂量组分别给予3 mg/mL达美康混悬液、2 g/mL TXL、1 g/mL TXL灌胃治疗,模型对照组给予生理盐水灌胃。治疗4周后处死,取血检测血糖、肌酸激酶(CK)、乳酸脱氢酶(LDH),切取心肌组织,免疫组化法检测TGF-β1表达情况。结果与模型对照组比较,TXL大剂量组血糖明显降低[(10.54±2.06)mmol/L比(23.16±5.74)mmol/L],CK、LDH明显升高[(120.57±18.83)U/mg比(78.26±12.01)U/mg,(5052.06±418.64)U/mg比(3784.15±349.62)U/mg];TGF-β1阳性染色颗粒的平均光密度(MOD)降低[(0.148±0.006)比(0.262±0.008)];差异均有高度统计学意义(均P<0.01)。结论 TXL对糖尿病大鼠有一定的降血糖作用,可减少心肌酶漏出,改善心肌能量代谢,同时降低心肌中TGF-β1的表达,减慢心肌组织纤维化进程,延缓和改善糖尿病心肌病的心肌损伤。
Objective To explore the effects of Tangxinle(TXL) on myocardial enzyme and transforming growth factor-β1(TGF-β1) in experimental rats with diabetic cardiomyopathy. Methods Diabetes model was established with streptozotocin by intraperitoneal injection in Sprague-Dawley rats, after 8 weeks diabetes cardiomyopathy model was formed, then diabetic cardiomyopathy rats were randomly divided into four groups: model control group, the Diamicron control group,TXL high-dose group, TXL small-dose group, 12 rats in each group, 10 normal rats were as the normal control group.Diamicron control group, TXL high-dose group, TXL small-dose group were given 3 mg/mL of Diamicron suspension,2 g/mL TXL, 1 g/mL TXL lavage treatment respectively, the model control group was given normal saline lavage. Rats of five groups were killed after 4 weeks treatment. Blood glucose, creatine kinase(CK) and lactic dehydrogenase(LDH)were detected, and the expression of TGF-β1in five groups were detected by immunohistochemistry method. Results Compared with model control group, TXL high-dose group fasting blood glucose decreased obviously [(10.54 ±2.06)mmol/L vs(23.16±5.74) mmol/L]; CK and LDH increased remarkably [(120.57±18.83) U/mg vs(78.26±12.01) U/mg;(5052.06±418.64) U/mg vs(3784.15±349.62) U/mg]; the average absorbance value of staining positive particles TGF-β1in myocardial cell reduced [(0.148±0.006) vs(0.262±0.008)], the differences were statistically significant(all P < 0.01).Conclusion TXL has a certain hypoglycemic effect on diabetic rats, it can reduce the myocardial enzyme leakage to improve the metabolic disorder of energy, meanwhile it can reduce the expression of TGF-β1to slow down fibrous degeneration in myocardial tissue and delay development of diabetic cardiomyopathy.
Objective To explore the effects of Tangxinle(TXL) on myocardial enzyme and transforming growth factor-β1(TGF-β1) in experimental rats with diabetic cardiomyopathy. Methods Diabetes model was established with streptozotocin by intraperitoneal injection in Sprague-Dawley rats, after 8 weeks diabetes cardiomyopathy model was formed, then diabetic cardiomyopathy rats were randomly divided into four groups: model control group, the Diamicron control group,TXL high-dose group, TXL small-dose group, 12 rats in each group, 10 normal rats were as the normal control group.Diamicron control group, TXL high-dose group, TXL small-dose group were given 3 mg/mL of Diamicron suspension,2 g/mL TXL, 1 g/mL TXL lavage treatment respectively, the model control group was given normal saline lavage. Rats of five groups were killed after 4 weeks treatment. Blood glucose, creatine kinase(CK) and lactic dehydrogenase(LDH)were detected, and the expression of TGF-β1in five groups were detected by immunohistochemistry method. Results Compared with model control group, TXL high-dose group fasting blood glucose decreased obviously [(10.54 ±2.06)mmol/L vs(23.16±5.74) mmol/L]; CK and LDH increased remarkably [(120.57±18.83) U/mg vs(78.26±12.01) U/mg;(5052.06±418.64) U/mg vs(3784.15±349.62) U/mg]; the average absorbance value of staining positive particles TGF-β1in myocardial cell reduced [(0.148±0.006) vs(0.262±0.008)], the differences were statistically significant(all P < 0.01).Conclusion TXL has a certain hypoglycemic effect on diabetic rats, it can reduce the myocardial enzyme leakage to improve the metabolic disorder of energy, meanwhile it can reduce the expression of TGF-β1to slow down fibrous degeneration in myocardial tissue and delay development of diabetic cardiomyopathy.
引文
[1]沈亚非,徐焱成.链脲佐菌素诱导实验性糖尿病大鼠模型建立的研究[J].实用诊断与治疗杂志,2005,19(2):79.
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[8]贡云华,蒋家雄,李泽,等.三七皂甙C1对四氧嘧啶糖尿病小鼠的降血糖作用[J].药学学报,1991,26(2):81-82.
[9]陈卫辉,钱华,王慧中.麦冬多糖对正常和实验性糖尿病小鼠血糖的影响[J].中国现代应用医学杂志,1998,16(4):26.
[10]高彦彬.中国糖尿病防治特色[M].哈尔滨:黑龙江科学技术出版社,1995:311-437.
[11]Sharma K,Ziyadeh FN.Hyperglycemia and diabetic kidney disease:the case for transforming growth factor-β1as a key mediator[J].Diabetes,1995,44:1139-1145.
[12]周月宏,王秋月.CTGF在糖尿病肾病发病机制中的作用及意义[J].国际内分泌杂志,2006,7(26):273.
[13]赵传志,邹华.糖尿病心肌病与心肌能量代谢[J].中外医学研究,2010,8(3):21-22.
[14]赵娜娜.糖尿病心肌病的治疗进展[J].医学综述,2013,19(3):502-504.
[15]张晓敏.TGF-β1/Smads信号通路与糖尿病心肌纤维化[J].医学综述,2012,18(11):1644-1647.
[2]范世平,饶振芳,马晓霖,等.糖心宁胶囊治疗糖尿病性冠心病的实验研究[J].新中医,2001,33(7):75-77.
[3]梁自文,张忠辉,张平,等.糖尿病性心肌病大鼠的心肌结构、代谢和功能的变化[J].第三军医大学学报,1996,(8):306-308.
[4]Bolzan AD,Bianchi MS.Genotoxicity of streptozotocin[J].Mutat Res,2002,512:221.
[5]段云燕,赵雯,张军.糖尿病心肌病发病机理研究进展[J].心血管病学进展,2011,32(4):524-527.
[6]廖永晖,汤雨,千年松,等.氧化应激与细胞凋亡[J].新乡医学院学报,2011,28(1):110-113.
[7]安荣,孔维,丁延平.糖心乐对糖尿病心肌病大鼠血糖心肌酶及心功能的影响[J].陕西中医,2012,33(9):1240-1243.
[8]贡云华,蒋家雄,李泽,等.三七皂甙C1对四氧嘧啶糖尿病小鼠的降血糖作用[J].药学学报,1991,26(2):81-82.
[9]陈卫辉,钱华,王慧中.麦冬多糖对正常和实验性糖尿病小鼠血糖的影响[J].中国现代应用医学杂志,1998,16(4):26.
[10]高彦彬.中国糖尿病防治特色[M].哈尔滨:黑龙江科学技术出版社,1995:311-437.
[11]Sharma K,Ziyadeh FN.Hyperglycemia and diabetic kidney disease:the case for transforming growth factor-β1as a key mediator[J].Diabetes,1995,44:1139-1145.
[12]周月宏,王秋月.CTGF在糖尿病肾病发病机制中的作用及意义[J].国际内分泌杂志,2006,7(26):273.
[13]赵传志,邹华.糖尿病心肌病与心肌能量代谢[J].中外医学研究,2010,8(3):21-22.
[14]赵娜娜.糖尿病心肌病的治疗进展[J].医学综述,2013,19(3):502-504.
[15]张晓敏.TGF-β1/Smads信号通路与糖尿病心肌纤维化[J].医学综述,2012,18(11):1644-1647.