紫檀芪对肥胖孕鼠肝脏脂代谢的影响_邢小芳.pdf

紫檀芪对肥胖孕鼠肝脏脂代谢的影响邢小芳，柏青，何飞敏，邵文璠，李春健，黄晶，华蕾，王永梅(云南省第三人民医院，云南 昆明 650011)摘要 目的观察紫檀芪对肥胖孕鼠糖脂代谢及肝脏组织中脂代谢基因成纤维细胞生长因子 21(FGF21)、CD36 和载脂蛋白 B(Aop B)表达的影响，以为其安全用于肥胖孕妇提供实验依据。方法取 60 只雌性和 30 只雄性清洁级昆明小鼠，选取 10 只雌性小鼠作为正常组，其余 50 只雌性小鼠采用高脂饮食喂养 2 个月构建肥胖模型。2 个月后，所有小鼠按照雄性和雌性 1 2 同笼喂养，次日检查小鼠受孕后，将肥胖孕鼠随机分为模型组和紫檀芪低、中、高剂量组，每组 12 只。受孕 4 d 后，正常组和模型组孕鼠给予生理盐水 1 mL 灌胃，紫檀芪低、中、高剂量组孕鼠分别给予 2 5mg/(kgd)、5 mg/(kgd)、10 mg/(kgd)紫檀芪悬混液灌胃，均连续灌胃 2 周。麻醉后腹主动脉取血检测血脂、血糖、胰岛素、胰岛素抵抗指数;取肝脏，HE 染色进行病理观察，免疫荧光染色和Western blot 法检测肝脏组织中 FGF21、CD36、Aop B 表达情况。结果与正常组比较，模型组孕鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL C)及血糖、胰岛素、胰岛素抵抗指数均明显升高(P 均 0 05)，血清高密度脂蛋白胆固醇(HDL C)水平明显降低(P 0 05);与模型组比较，紫檀芪各组孕鼠血清 TG、TC、LDL C 水平及血糖、胰岛素、胰岛素抵抗指数均明显降低(P 均 0 05)，血清 HDL C 水平均明显升高(P 均 0 05)。HE 染色见正常组肝细胞大小均一，细胞核基本位于细胞中央，模型组有明显脂肪空泡，紫檀芪各组病理改变较模型组轻。与正常组比较，模型组孕鼠肝脏组织中 FGF21 和 CD36 相对表达量明显升高(P 均 0 05)，Apo B 相对表达量明显降低(P 0 05);与模型组比较，紫檀芪各组孕鼠肝脏组织中 FGF21 和 CD36 相对表达量均明显降低(P 均 0 05)，Apo B 相对表达量均明显升高(P 均 0 05)。结论紫檀芪可调节肥胖孕鼠糖脂代谢，其机制可能与调节肝脏组织中 FGF21、CD36 和 Apo B 表达有关。关键词 肥胖;脂代谢;紫檀芪;孕鼠;成纤维细胞生长因子 21;CD36;载脂蛋白 Bdoi:10 3969/j issn 1008 8849 2022 22 008 中图分类号 332 文献标识码 A 文章编号 1008 8849(2022)22 3106 06 作者简介 邢小芳，女，主治医师，主要研究方向为妊娠期相关疾病。通信作者 王永梅，E mail:460335241 qq com 基金项目 昆明市科技计划项目(2017 1 S16730)Effect of pterostilbene on liver lipid metabolism in obese pregnant ratsXING Xiaofang，BAI Qing，HE Feimin，SHAO Wenfan，LI Chunjian，HUANG Jing，HUA Lei，WANG Yongmei(The Third People s Hospital of Yunnan Province，Kunming 650200，Yunnan，China)Abstract:Objective It is to observe the effect of pterostilbene on glucolipid metabolism and the expression of lipidmetabolism genes fibroblast growth factor 21(FGF21)，CD36 and apolipoprotein B(Aop B)in liver tissues of obese preg-nant rats，in order to provide an experimental basis for its safe use in obese pregnant women Methods Sixty female and 30male clean grade Kunming mice were selected，in which 10 female mice were selected as the normal group，and the other50 female mice were fed with high-fat diet for 2 months to establish obesity models After 2 months，all mice were fed in thesame cage according to male and female 12 After checking the mice for conception on the next day，the obese pregnantmice were randomly divided into the model group and the low，medium and high dose groups of pterostilbene，with 12 micein each group After 4 days of pregnancy，the pregnant rats in the normal group and model group were given 1 mL normalsaline by gavage，and the pregnant rats in the low，middle and high dose groups of pterostilbene were given 25 mg/(kgd)，5 mg/(kgd)，and 10 mg/(kgd)pterostilbene suspension by gavage，respectively，all gavaged for 2 weeks The bloodwas collected from the abdominal aorta after anesthesia to detect blood lipids，blood glucose，insulin and insulin resistance6013现代中西医结合杂志 Modern Journal of Integrated Traditional Chinese and Western Medicine 2022 Nov，31(22)index;The livers were taken for pathological observation by HE staining，and the expression of FGF21，CD36 and Aop B inliver tissue was detected by immunofluorescence staining and Western blot esults Compared with the normal group，thelevels of serum total cholesterol(TC)，triglyceride(TG)，low density lipoprotein cholesterol(LDL-C)，blood glucose，insulin and insulin resistance index of pregnant rats in the model group were significantly increased(all P 0 05)，whilethe level of serum high density lipoprotein cholesterol(HDL-C)was significantly decreased(P 0 05);Compared withthe model group，the levels of serum TG，TC，LDL-C，blood glucose，insulin and insulin resistance index of pregnant ratsin each dose group of pterostilbene were significantly decreased(all P 0 05)，and the level of serum HDL-C was signifi-cantly increased(P 0 05)HE staining showed that the hepatocytes in the normal group were uniform in size and the nu-cleus was basically located in the center of the cell，while there were obvious fat vacuoles in the model group，and the path-ological changes in each group of pterostilbene were lighter than those in the model group Compared with the normalgroup，the relative expression of FGF21 and CD36 in the liver tissue of pregnant rats in the model group were increased sig-nificantly(all P 0 05)，and the relative expression of Apo B was decreased significantly(P 0 05);Compared with themodel group，the relative expression of FGF21 and CD36 in the liver tissue of pregnant rats in each dose group of pterostil-bene was significantly decreased(all P 0 05)，and the relative expression of Apo B was significantly increased(P 0.05)Conclusion Pterostilbene can regulate glucolipid metabolism in obese pregnant rats，and its mechanism may be re-lated to regulating the expression of FGF21，CD36 and Apo B in liver tissueKeywords:obesity;lipid metabolism;pterostilbene;pregnant rats;fibroblast growth factor 21;CD36;apolipoprotein B妊娠后女性体重会大幅增加，只要没有超出标准范围，一般不会造成不良影响，但如果孕妇过度肥胖，会给自身和胎儿带来不利影响。对孕妇自身而言，过度肥胖可引起难产、胎儿死亡等，产后可诱发高血糖、高血脂、高血压等1 2。对胎儿可导致发育迟缓，甚至引起新生儿神经管缺陷，另外胎儿在长大后相较于正常人也容易发生肥胖、高血脂、高血压等3 4。目前对于妊娠期肥胖的治疗以锻炼和控制饮食为主，但是多数孕妇依从性较差;部分肥胖孕妇使用辛伐他汀和二甲双胍治疗5，但均有不良反应，耐受性较差，因此开发安全的药物用于妊娠期肥