CAJ | 학술논문

观察葛根素(Puerarin)对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠心肌细胞的保护作用,并探讨血小板反应素1(Thrombospondin一1,TSP-1)的表达改变及其作用.雄性SD大鼠45只随机分为三组(n=15):糖尿病组和葛根素治疗组采用一次腹腔注射链脲佐茵素(STZ)65 mg/kg制备糖尿病模型,其中葛根素治疗组于造模后葛根素腹腔注射4周(100 mg/kg/day),正常对照组仅腹腔注射等量生理盐水(6 ml/kg).同样喂养4周.四周后各组大鼠处死,H-E染色及透射电子显微镜观察三组大鼠心肌细胞纤维显微结构和超微结构的病理改变,免疫组化和实时荧光定量PCR法观察大鼠心肌细胞中TSP-1蛋白和mRNA表达的变化.同时利用Langendorff离体心脏灌流法测定各组大鼠心室肌细胞功能.结果发现葛根素治疗组较糖尿病组大鼠的体重增加明显,同时血糖下降,有显著性差异(P<0.01).H-E染色显示糖尿病大鼠多处心肌肌丝紊乱伴少量炎症细胞浸润,电镜下发现有线粒体嵴消失溶解.肌丝排列紊乱等病理改变,而葛根素治疗组大鼠偶见上述病理变化.免疫组化显示葛根素治疗组心肌内TSP-1阳性细胞密度小于糖尿病大鼠.TSP-1 mRNA表达也比糖尿病大鼠要低.此外葛根素治疗组大鼠的左室收缩末压(LVSEP)、左心室舒张末期压(LVEDP)等心功能指标均明显低于正常组(P<O.01),但较糖尿病组有显著改善(P<O.01).上述结果显示葛根素能保护糖尿病大鼠心肌细胞的高糖损伤和维持心室肌细胞的功能,而该机制可能与抑制心肌细胞TSP-1表达的水平有关.
관찰갈근소(Puerarin)대련뇨좌균소(streptozotocin,STZ)유도적당뇨병대서심기세포적보호작용,병탐토혈소판반응소1(Thrombospondin일1,TSP-1)적표체개변급기작용.웅성SD대서45지수궤분위삼조(n=15):당뇨병조화갈근소치료조채용일차복강주사련뇨좌인소(STZ)65 mg/kg제비당뇨병모형,기중갈근소치료조우조모후갈근소복강주사4주(100 mg/kg/day),정상대조조부복강주사등량생리염수(6 ml/kg).동양위양4주.사주후각조대서처사,H-E염색급투사전자현미경관찰삼조대서심기세포섬유현미결구화초미결구적병리개변,면역조화화실시형광정량PCR법관찰대서심기세포중TSP-1단백화mRNA표체적변화.동시이용Langendorff리체심장관류법측정각조대서심실기세포공능.결과발현갈근소치료조교당뇨병조대서적체중증가명현,동시혈당하강,유현저성차이(P<0.01).H-E염색현시당뇨병대서다처심기기사문란반소량염증세포침윤,전경하발현유선립체척소실용해.기사배렬문란등병리개변,이갈근소치료조대서우견상술병리변화.면역조화현시갈근소치료조심기내TSP-1양성세포밀도소우당뇨병대서.TSP-1 mRNA표체야비당뇨병대서요저.차외갈근소치료조대서적좌실수축말압(LVSEP)、좌심실서장말기압(LVEDP)등심공능지표균명현저우정상조(P<O.01),단교당뇨병조유현저개선(P<O.01).상술결과현시갈근소능보호당뇨병대서심기세포적고당손상화유지심실기세포적공능,이해궤제가능여억제심기세포TSP-1표체적수평유관.
To investigate the myocardial protective effects of puerarin on streptozotoein(STZ)-induced diabetic rats and the possible mechanism were involved.45 Sprague-Dawley male rats wererandomly divided into 3 groups as diabetic group(intraperitoneally injected STZ 65 ms/ks),puerarin treatment group(intraperitoneally injected STZ 65 ms/ks,and intraperitoneally injected puerarin 100 mg/kg/day for 4 weeks),and control group(intraperitoneally injected saline 6 ml/kg).Four weeks after the model induction,the myocardial changes were observed by H-E stain and Transmission electron microscopy,the alteration of thrombospondin-1(TSP-1)protein and mRNA expression in the myocardium were also assessed by immunohistochemistry and real-time PCR. The heart function of three groups' rats was tested by Langendorff isolated in vivo heart perfusion. The differences in the data of weight and blood sugar of diabetic between puerarin treatment and normal groups were significant after 4 weeks (P<0.O1). Our results demonstrated that diabetic myocardial ultrastructural changes included myofibrillar disarrangements and mitochondria disruption. These damages were significantly less severe in the puerarin treatment group compared with the diabetic group. A significant decrease of TSP-1 expression was observed in the puerarin treated rats' myocardium compared to the diabetic rats (P<O.01). Left ventricular systolic end pressure (LVSEP)and left ventricular developed pressure (LVDP) of puerarin treatment group were also significantly increased compared to diabetic group (P<O.O1). Altogether puerarin could improve the left ventricular function of diabetic rats and showed protective effects of myocardium by decreasing the TSP-1expression in myocardium of diabetic rats.