丹参多酚酸盐对糖尿病心肌病保护作用及可能机制

Protective effect and possible mechanisms of salvianolate in diabetic cardiomyopathy

目的探讨丹参多酚酸盐对糖尿病心肌病保护作用及其可能机制。方法 40只健康雄性wistar大鼠随机分成4组,正常对照组(Normal control,NC)、糖尿病对照组(Diabetic control group,DC)、丹参多酚酸盐高剂量(15 mg·kg-1)治疗组(High-dose treatment group,HT)及低剂量(5 mg·kg-1)治疗组(Low-dose treatment group,LT),每组10只,其中3组(DC、HT、LT)大鼠给予腹腔注射链脲佐菌素诱发糖尿病模型。建模后第7天开始给予治疗组丹参多酚酸盐腹腔注射,NC及DC组大鼠给予相同体积生理盐水注射。给药8周后超声多普勒检测大鼠心功能,转移酶介导的缺口末端标记法(TUNEL法)检测心肌细胞凋亡,免疫组织化学法检测心肌细胞Bcl-2、Caspase-3表达。结果与NC组比较,DC组凋亡心肌细胞数增多(P<0.05),Bcl-2表达减弱(P<0.05),Caspase-3表达增强(P<0.05);与DC组比较,治疗组凋亡细胞数减少(P<0.05),Bcl-2表达增强(P<0.05),Caspase-3表达减弱(P<0.05);应用丹参多酚酸盐治疗后,可有效改善心功能,HT组较LT组作用更加明显,差异具有统计学意义(P<0.05)。结论糖尿病组大鼠心功能明显下降,丹参多酚酸盐通过增强Bcl-2表达,抑制Caspase-3表达,阻遏心肌细胞凋亡,改善心功能,高剂量丹参多酚酸盐的作用更加明显。

Objective To explore salvianolate protective effect and the possible mechanism of diabetic cardiomyopathy in diabetic rats. Methods Forty rats were randomly divided into normal control, diabetic control group,low-dose salvianolate （5 mg . kg^-1 . d^-1 ）treat ment group and high-dose salvianolate （ 15 mg . kg ^- 1 . d ^- 1 ） treatment group （ n = 10 ） , wherein the three groups （ DC, HT, LT） diabetic animal models were induced by intraperitoneal injection streptozotocin（STZ）. After the models were constructed successfully, in treatment group salvianolate was given by intraperitoneal injection, NC and DC rats were given saline. Eight weeks later, heart function was detected by Doppler echocardiography, and transferase-mediated nick end labeling （TUNEL method）was used to detect cardiac myocyte apopto sis, and immnnohistochemical staining used to detect the level of Bcl-2, Caspase-3. Results Compared with＂ NC group, DM group （PC） rat cardiac myocyte apoptosis was significantly increased（ P 〈 0.05 ） ;Bcl-2 expression was decreased（ P 〈 0.05 ） ;Caspase-3 expression was significantly increased （ P 〈 0.05 ）. In treatment group, compared with the DM group, the number of apoptotie cells reduced （ P 〈 0. 05 ）, Bcl-2 expression increased （ P 〈 0.05 ）, Caspase-3 expression diminished （ P 〈 0.05 ）. After the salvianolate treatment, which can ef fectively improve heart function, the role of HT group was more obvious than that of the LT group,with statistically significant difference （P 〈 0.05 ）. Conclusions The heart function of diabetic control group is significantly decreased. Salvianolate can improve the heart function by enhancing the exPression of Bcl-2, and inhibiting Caspase-3 expression, and reduce myocardial apoptosis, which is more obvi- ous in high-dose group.