银杏叶提取物对脂质诱导胰岛素抵抗大鼠模型的干预性研究

Intervention study of Ginkgo Biloba extract on vascular endothelial cell damage in a rat model of lipid-induced insulin resistance

目的通过喂养特殊高脂饮食建立胰岛素抵抗（IR）大鼠模犁，并设立正常组、银杏叶组、阳性药物组（文迪雅），进行相关的血液生化、放免检查、血管内壁形态学观察，旨在探讨IR与糖脂代谢、血管内皮功能障碍之间的相互关系，同时为银杏叶制剂用于早期预防IR相关的心血管疾病和进一步治疗提供实验依据。方法选取健康成年SD雄性大鼠40只，体重200～250g，适应性饲养1周后将大鼠编号，按照随机数字表将大鼠分人正常组（n=10）、模型组（n=10）、银杏叶组（n=10）、阳性药物组（n=10）；每周监测大鼠的血糖和体重，干预12周后处死动物，收集血液，进行一系列血液生化指标检测（FBG、2hPG、FINS、PINS、血脂、NO／NOS、ET－1、AngⅡ）；并计算胰岛素敏感指数（ISI）值，评估造模是否成功；然后进行血管内壁的形态学观察；最后进行有关的统计学分析。结果（1）与对照组比较，模型组胰岛素敏感指数（ISI）值下降，血糖、血脂水平升高，差异有统计学意义（P〈0．05或P〈0．01）；与模型组比较，银杏叶组、阳性药物组的ISI值升高，血糖、血脂水平下降，差异有统计学意义（P〈O．05或P〈0．01）。（2）与对照组比较，模型组血浆ET－1、AngⅡ水平升高，血浆NO水平降低，差异有统计学意义（P〈0．05或P〈0．01）；与模型组比较，银杏叶组、阳性药物组的血浆ET－1、AngⅡ水平降低，血浆NO水平提高，差异有统计学意义（P〈0．05）。（3）光镜下观察，模型组大鼠的主动脉血管壁局限增厚，可观察到泡沫细胞，第4个月时已形成脂质条纹，形成典型的粥样斑块，符合动脉粥样硬化的早期病理改变，银杏叶组大鼠的主动脉血管壁脂质条纹有明显改善。结论（1）胰岛素抵抗可导致血管内皮功能障碍，NO与ET－1、AngⅡ之间的不平衡与内皮功能障碍互为因果，共同参与心血管疾病的发生。（2）银杏叶提取物能够改善IR大鼠的糖脂代谢，并对血管内皮功能具有一定的保护作用。（3）银杏叶提取物可部分或逆转IR所致的内皮功能障碍，对IR可能存在相应的干预机制。

Objective To investigate the correlation between insulin resistance and glucolipid metabolism and vascular endothelial dysfunction, and to provide experimental evidence of Ginkgo on early-stage prevention of insulin resistance related cardiovascular diseases in a rat model of insulin resistance induced by a special high-lipid diet. Methods Fourty male SD rats （200-250g） were equally randomized to four groups： normal control group, model control group, Ginkgo group, and rosiglitazone group. Blood samples were collected and serum biochemical indicators, free blood glucose （FBG）, 2 h post-glucose （2hPG）, FINS, PINS, serum lipid, Nitro Oxide system （NOS）, endothelin-1 （ET-1） and angiotensin II （AngII）, were detected. Insulin sensitive index （ISI） was used to evaluate whether the model was successfully created. The aortic wall was obtained for morphological observation of the vascular inner wall. Related statistical analysis was also performed. Results （1） Compared with normal control group, ISI significantly decreased, serum glucose and lipid significantly increased in the model control group （P 〈 0.05 or P 〈 0.01）. Compared with the model control group, ISI significantly increased, serum glucose and lipid significantly decreased in both Ginkgo and rosiglitazone groups （P 〈0.05 or P 〈0.01）. （2） Compared with the control group, NO decreased significantly while ET-1 and AngII increased significantly in the model control group （P 〈0.05 or P 〈0.01）. Compared with the model control group, NO increased significantly while ET-1 and AngII decreased significantly in both Ginkgo and rosiglitazone groups （P 〈0.05）. （3） Local thickness in the aortic wall and foam cells were seen by optical microscopy. Fatty streaks emerged and typical athesclerotic plaques existed in the fourth month, which exhibited early-stage injuries of arterial atherosclerosis. Fatty streaks in the aortic wall were improved significantly in Ginkgo group. Conclusions （1） Insulin resistance may lead to endothelial dysfunction. Endothelial dysfunction interacts with imbalance between NO, ET-1 and AnglI, which may play a role in the process of cardiovascular disease. （2） Ginkgo biloba extract can improve glucolipid metabolism in insulin resistance rats and may have a protective effect on endothelial function of blood vessels. （3） Ginkgo biloba extract can partly or significantly reverse endothelial dysfunction due to insulin resistance, and may have related intervention on insulin resistance.