白藜芦醇对小鼠营养性肥胖伴生殖功能损害的作用

Role of resveratrol in diet-induced obesity and reproductive insufficiency in mice

目的探讨白藜芦醇对肥胖性不育的防治作用。方法36只雌性昆明小鼠按随机区组法分为3组（对照组、高脂组和干预组），每组12只，分别喂以正常饮食、高脂饮食和高脂饮食加白藜芦醇。分别在4周、8周和12周时监测动物体重、空腹血糖和糖耐量情况。喂养12周后检测小鼠空腹胰岛素、血清雌二醇、黄体生成素、睾酮水平，以阴道脱落细胞判断小鼠动情周期，以雌、雄个体3：1的比例进行交配，观察小鼠生育能力。结果喂养12周后高脂组和干预组小鼠体重[（61．52±6．92），（63．06±5．80）g]都明显高于对照组[（47．76±5．02）g]，差异具有统计学意义（P〈0．05）；而干预组体重相对于高脂组差异没有统计学意义（P〉0．05）。高脂组空腹血糖[（6．98±0．33）mmol／L]和空腹胰岛素[（38．02±7．21）μIU／L]明显高于对照组[（5．30±0．36）mmol／L，（30．29±5．58）μlU／L]，差异均具有统计学意义（P〈0．05）；干预组空腹血糖[（5．45±0．67）mmol／L]和空腹胰岛素[（30．21±4．60）μIU／L]与高脂组相比明显下降，且差异均具有统计学意义（P〈0．05）。性激素分析显示高脂组雌二醇[（5．67±0．98）ng／L]与黄体生成素l（0．346±0．025）IU／L]较对照组[（3．007±0．721）ng／L，（0．202±0．041）IU／L]明显升高（P〈0．05）；干预组雌二醇[（2．115±0．353）ng／L]和黄体生成素[（0．245±0．041）IU／L]与高脂组相比明显下降，差异均具有统计学意义（P〈0．05）。睾酮含量各组之间没有统计学差异。高脂饮食还导致动情周期紊乱甚至消失，卵巢组织学显示高脂饮食导致闭锁卵泡数量明显增加。结论高脂饮食能够诱导雌性小鼠肥胖、代谢综合征与生殖功能榻害．白藜芦醇对此能起到一定缓解作用。

Objective To investigate the role of reselweratrol in rescue of obesity-induced infertil- ity. Methods According to randomized block design, thirty-six female Kunming mice were randomly divided into three groups （control group, high-fat group and treatment group） , and twelve in each group. Three groups were fed with a standard rodent chow, a high-fat diet, or a high-fat diet plus resveratrol, respectively. Body weight, fasting blood glucose, and an intraperitoneal glucose tolerance test were determined at 4th, 8th, and 12th week. At the 12th week,fasting insulin, estrogen,lnteinizing hormone, and testosterone were measured. The number of vaginal exfoliated cells was counted to determine the estrous cycle of mice. Three female mice were mated with a male in order to assess mice fertility. Results After 12 weeks of feeding, the body weights of high-fat group [ （61.52 ± 6.92 ） g ] and treatment group [ （ 63.06 ± 5.80 ） g ] were significantly higher than that in control group [ （ 47.76 ± 5.02 ） g], and had statistical difference （ P 〈 0.05 ）, while the body weights between high-fat group and treatment group had no differences （ P 〉 0. 05 ）. Fasting blood glucose [ （6.98 ±0.33） mmol/L] and fasting insulin [ （38.02 ±7.21 ） μIU/L]in high-fat group were significandyhigher than those of control group [ （5.30 ±0.36） mmol/L, （30.29 ±5.58） μIU/L,P 〈0.05 ]. Compared with high-fat group, fasting blood glucose [ （ 5.45 ± 0.67 ） mmol/L ] and fasting insulin [ （ 30.21 ± 4.60 ） μIU/L ] of treatment group were decreased significantly （P 〈 0.05 ）. Estrogen [ （5.67 ± O. 98 ） ng/L ] and luteinizing hormone [ （ 0. 346 ± 0. 025） IU/L ] of high-fat group were significantly increased than those of control group [ （3. 007 ± 0. 721 ） ng/L, （0. 202 ± 0. 041 ） IU/L, P 〈 0.05 ]. Estrogen [ （2.115 ± 0. 353 ） ng/L] and luteinizing hormone [ （0.245 ± 0. 041 ） IU/L] in treatment group were decreased significantly compared with high-fat group （ P 〈 0.05 ）. Testosterone levels among the groups had no significant differ- ences. The high-fat diet also caused a disordered or even an absence of estrous cycle. Ovarian histology showed a marked increase in the number of atretic follicles in high-fat group. Conclusions High-fat diet could induce obesity, signs of metabolic syndrome, and partial reproductive impairment in female Kuming mice. Also, reseveratrol may have beneficial effects in preventing obesity-induced infertility.