成年大鼠接受高脂或热量限制饮食对其衰老后身体构成、糖脂代谢及胰岛内β、α细胞分泌功能影响的比较研究

目的通过对成年大鼠给予高脂饮食（HFD）或能量限制饮食（CRD）干预至老年期，比较糖脂代谢指标及胰岛细胞内胰岛素，胰高糖素分泌功能的变化，探讨热量摄入在衰老伴胰岛素抵抗中的作用机制。方法14～16月龄雄性SD大鼠45只分别给予高脂饮食（热量为5．86kcal／kg，以脂肪供能为主，占总热量的43．27％），正常饮食（热量为3．2kcal／kg）及限制能量摄入（热量为1．6kcal／kg），分别在干预0，8，16周时检测大鼠的体质量，腹腔脂肪，体脂比，空腹血糖（FBG）、甘油三脂（TG）、胆固醇（TC）、血浆游离脂肪酸（FFA）及血浆胰岛素水平，并根据FBG和空腹胰岛素计算稳态胰岛素抵抗指数（HOMA—IR）、HOMA-β和胰岛素敏感性（ISI）。应用免疫组化方法检测胰岛内胰岛素及胰高血糖素分泌及表达量的变化。结果（1）成年大鼠衰老过程中，体质量、腹腔脂肪、体脂比、FFA、TG、FBG及胰岛素均随年龄的增加而升高；由此计算的HOMA—IR升高，ISI和HOMA-β降低，但差异无统计学意义。胰岛细胞内胰岛素／胰高血糖素的水平和胰岛D凤的面积未见明显变化。（2）HFD组大鼠16周时，HOMA—IR明显上升，ISI明显降低，体质量、腹腔脂肪、体脂比显著增加，FFA显著升高，血胰岛素、胰岛内胰岛素和胰高血糖素分泌量增多，差异均有统计学意义（P〈0．05）。（3）CRD干预时HOMA。IR显著降低，ISI和HOMA—p显著升高；体质量、腹腔脂肪显著降低（P〈0．05），空腹血糖及胰岛素降低、血浆FFA，TG，TC水平降低；胰岛内胰岛素和胰高血糖素的表达水平亦显著性降低。结论SD大鼠出现胰岛素抵抗、胰岛素敏感性和胰岛13细胞分泌功能下降等增龄变化，因自成年期开始HFD干预而进一步恶化，因CRD干预显著改善；FFA是增龄过程中受HFD或CRD的影响早且变化最持久的因子；HFD以胰岛素分泌增高为主，作用靶点可能主要在胰岛D细胞，而CRD以降低胰高血糖素为主，作用靶点侧重于α细胞。

A comparative study of high-fat diet and calorie restrict diet from adulthood on body composition, metabolic profile, morphology and secretary status of islet pla cells during aging in rats

Objective To observe the changes of body composition, metabolic profile, and morphology and secretary status of islet 13/a cells with high-fat diet （HFD, calorie is 5.86kcal/kg） and calorie restrict diet （CRD, calorie is 1.6kcal/kg） from middle adulthood to later adulthood. Methods A total of 45 male SD rats, 14 to 16 months of age were randomly divided into normal diet （ND）, HFD and CRD groups. At 0（14-16 months）, 8（16-18 months）, 16（18-20months） weeks, body weight （BW）, visceral fat, body fat ratio were measured as body composition; blood was collected to detect triglyceride and cholesterol as lipid profile, as well as free fatty acid （FFA）, fasting blood glucose and insulin. HOMA-IR, HOMA-13 and ISI were calculated according to the levels of fasting glucose and insulin. The secretary status of insulin and glucagon in islet were assessed by immunohistochemistry, and the area of ct/13-cell was measured. Results In adult rats, BW, visceral fat, body fat ratio, lipid profile, FFA, fasting glucose and insulin were increased with aging, meanwhile HOMA-IR increased while HOMA-13 and ISI were decreased （P 〉 0.05）, and the areas and levels of insulin and glucagon within islet had no significant change. In HFD group, BW, visceral fat, body fat ratio, triglyceride, FFA, fasting glucose and insulin were significantly increased during the 16 weeks, HOMA-IR was increased while ISI decreased, and levels of insulin and glucagon within islet were dramatically increased（P 〈 0.05）. In CRD group, BW, visceral fat, body fat ratio, triglyceride, FFA, fasting glucose, insulin and HOMA-IR were all decreased, while HOMA-13 and ISI were increased, and levels of insulin and glucagon within islet were dramatically decreased（P 〈 0.05）. Conclusion The age-related changes of increased insulin resistance, decreased insulin sensitivity were deteriorated by HFD, and improved by CRD. FFA was the earliest and most common impact factor in both HFD and CRD. As insulin levels in both serum and islet were increased in HFD group at 8 weeks, islet glucagon levels was decreased significantly at the same time in CRD group, β cell was the targeted cells by HFD whereas ct cells by CRD.