橙皮素纳米粒对大鼠糖尿病心肌病的预防作用

目的： 研究橙皮素（HSP）纳米粒对大鼠糖尿病心肌病（DCM）的预防效果。 方法： 应用注入法准备包载 HSP 的纳米粒，并进行质量检测。腹腔注射链脲佐菌素（STZ）建立大鼠Ⅰ型糖尿病（DM）动物模型，并将其分 为正常对照组、DM 组、HSP 溶液组及HSP 纳米粒组，应用超声心功能检测在体评价各组大鼠心功能，应用H-E 染色离体评价各组大鼠心肌组织病理特征。酶联免疫吸附剂法（ELISA）及免疫印迹检测HSP 预防DCM 的作用机 制。结果： HSP-NPs 分散均匀，包封率达（91.23±5.23）%。相比于正常对照组，DM 组大鼠心肌左室收缩末期 内径（LVESD）、左室舒张末期内径（LVEDD）值显著升高，左心室射血分数（LVEF）、舒张早期与舒张晚期最 大运动速度比值（E/A）和左室短轴缩短率（LVFS）值显著降低，同时心肌细胞排列紊乱、心肌纤维断裂。相比 于DM 模型及HSP 溶液组，HSP 纳米粒组LVESD、LVEDD 值显著下降，LVEF、E/A 和LVFS值显著升高，心肌 细胞形态接近正常对照组大鼠。ELISA 法及免疫印迹检测结果显示，与正常对照组比较，DM 组大鼠心肌超氧化 物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSP-Px）含量及B淋巴细胞瘤-2（Bcl-2）含量显著下降，同时丙二醛 （MDA）含量、半胱氨酸蛋白酶-3（caspase-3）及Bcl 相关X 蛋白（Bax 蛋白）表达显著升高。与DM 组及HSP 溶 液组比较，HSP 纳米粒组大鼠心肌SOD、GSP-Px 含量及Bcl-2 含量显著上高，同时MDA 含量、caspase-3 及Bax 蛋白表达显著下降。结论： 应用纳米粒包载HSP 能增加药物的溶解度及稳定性，显著提高药物在体应用的生物利 用度，增加HSP 的治疗效果，从而通过抑制氧化应激损伤引起的细胞凋亡发挥抗DCM 的作用

The preventive effect of hesperidin nanoparticles on diabetic cardiomyopathy in rats

Objective To investigate the preventive effect of hesperidin （HSP） nanoparticles on diabetic cardiomyopathy（ DCM） and their mechanism. Methods HSP loaded nanoparticles（ HSP-NPs） were prepared by injection method and their qualities were investigated. The type I diabetes（ DM） animal model was established by intraperitoneal injection of a single large dose of streptozotocin（ STZ）. The rats were randomly divided into a normal control group， a DM group， an HSP solution group， and an HSP nanoparticle group， and then received corresponding forms of drug treatment intervention. After the drug intervention， the cardiac function of rats in each group was evaluated by ultrasound in vivo， and the pathological characteristics of the cardiac tissue of rats in each group were evaluated by H-E staining in vitro. ELISA and Western blot analysis were used to evaluate the mechanisms of HSP preventing DCM. Results The HSP-NPs was uniformly dispersed with a encapsulation rate as high as（ 91.23±5.23）%. Ultrasound heart function test and H-E staining results showed that compared with the normal control group， LVESD and LVEDD of DM group were significantly increased， LVEF， E/A and LVFS values were significantly decreased， and the myocardial cells were disordered， and the myocardial fibers were broken. Compared with DM model and HSP solution group， LVESD and LVEDD values of HSP nanoparticle group were significantly decreased， LVEF， E/A and LVFS values were significantly increased， the myocardial cells were arranged regularly， the myocardial tissue was complete ， and the morphology was close to that of normal control rats. ELISA and Western blotting analysis showed that compared with the normal control group， the contents of SOD， GSP-Px and Bcl-2 in myocardium of DM group were significantly decreased， and MDA content， caspase-3 and Bax protein expression were significantly increased. Compared with the DM group and HSP solution group， the contents of SOD， GSP-Px and Bcl-2 in myocardium of rats in HSP nanoparticle group were significantlyhigher， and MDA content， caspase-3 and Bax protein expression were significantly decreased. Conclusion Encapsulation of HSP with nanoparticles can increase the solubility and stability of drug， significantly improve the bioavailability of drug in vivo， increase the therapeutic effect of HSP， and thus play a role in the prevention of DCM by inhibiting the apoptosis caused by oxidative stress injury .