基于Ngn3和Caspase-3探讨姜黄素对宫内发育迟缓仔鼠胰腺发育及糖脂代谢的影响  

Exploration of the Effects of Curcumin on Pancreatic Development and Glucolipid Metabolism in Newborn Rats with Intrauterine Growth Retardation Based on Ngn3 and Caspase-3

作　　者：刘晓玲 雷小平 张莲玉 LIU Xiao-Ling;LEI Xiao-Ping;ZHANG Lian-Yu(Dept.of Neonatology,The Affiliated Hospital of Southwest Medical University,Luzhou 646000 Sichuan,China)

机构地区：[1]西南医科大学附属医院新生儿科,四川泸州646000

出　　处：《广州中医药大学学报》2022年第10期2361-2367,共7页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：四川省卫生和计划生育委员会科研课题项目(编号:18JP043)。

摘　　要：【目的】观察宫内发育迟缓(IUGR)仔鼠的胰腺发育及糖脂代谢情况及姜黄素的干预机制。【方法】采用日粮限饲的方法构建IUGR新生大鼠模型。将20只健康仔鼠分为健康组(健康仔鼠+基础饲料)、健康+姜黄素组(健康仔鼠+姜黄素+基础饲料),20只IUGR仔鼠分为IUGR组(IUGR仔鼠+基础饲料)和IUGR+姜黄素组(IUGR仔鼠+姜黄素+基础饲料)。给药结束后,检查仔鼠血糖、血脂水平,采用苏木素-伊红(HE)染色法观察胰腺发育情况,末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法测定胰岛β细胞凋亡率,免疫组织化学法、蛋白免疫印迹(Western Blot)法分别检测胰腺组织中Ngn3、Caspase-3阳性细胞数、蛋白表达水平。【结果】(1)与健康组比较,IUGR组仔鼠空腹血糖、总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)水平均升高,高密度脂蛋白胆固醇(HDL-C)水平降低(均P<0.05);与IUGR组比较,IUGR+姜黄素组仔鼠空腹血糖、TC及LDL-C水平降低,HDL-C水平升高(均P<0.05)。(2)与健康组比较,IUGR组仔鼠胰腺发育不完善;与IUGR组比较,IUGR+姜黄素组仔鼠胰腺发育较完善。(3)与健康组比较,IUGR组胰岛β细胞凋亡率升高(P<0.05);与IUGR组比较,IUGR+姜黄素组胰岛β细胞凋亡率降低(P<0.05)。(4)与健康组比较,IUGR组胰腺组织Ngn3阳性细胞数及蛋白表达水平降低,Caspase-3阳性细胞数及蛋白表达水平升高(均P<0.05);与IUGR组比较,IUGR+姜黄素组胰腺组织Ngn3阳性细胞数及蛋白表达水平升高,Caspase-3阳性细胞数及蛋白表达水平降低(均P<0.05)。此外,健康+姜黄素组上述各指标水平与健康组比较,差异均无统计学意义(P>0.05)。【结论】IUGR仔鼠存在糖脂代谢紊乱、胰腺结构发育不完善及胰岛β细胞凋亡加剧,姜黄素能够调节糖脂代谢,改善胰腺发育,这可能与其上调Ngn3活性和抑制Caspase-3表达相关。Objective To observe the pancreatic development and glucolipid metabolism in newborn rats with intrauterine growth restriction(IUGR)and the intervention mechanism of curcumin.Methods A newborn rat model of IUGR was constructed by daily dietary restriction.Twenty healthy newborn rats were divided into the healthy group(healthy newborn rats+basal diet)and the healthy+curcumin group(healthy newborn rats+curcumin+basal diet),while 20 IUGR newborn rats were divided into the IUGR group(IUGR newborn rats+basal diet)and IUGR+curcumin group(IUGR newborn rats+curcumin+basal diet).After ending the administration,the blood glucose and lipid levels of the newborn rats were detected,the pancreatic development was observed by hematoxylin-eosin(HE)staining,the apoptosis rate of pancreaticβ-cells was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)method,and the number of Ngn3 and Caspase-3 positive cells and protein expression levels of Ngn3 and Caspase-3 in pancreatic tissues were measured by immunohistochemistry and Western Blot,respectively.Results(1)Compared with the healthy group,the levels of fasting blood glucose,TC,LDL-C in the IUGR group were increased and the level of HDL-C was decreased(all P<0.05);compared with IUGR group,the levels of fasting blood glucose,TC,LDL-C in IUGR+curcumin group were decreased and the level of HDL was increased(all P<0.05).(2)Compared with the healthy group,the pancreatic development was incomplete in IUGR group;compared with IUGR group,the pancreatic development was more complete in IUGR+curcumin group.(3)Compared with the healthy group,the apoptosis rate of pancreatic isletβcells was increased in the IUGR group(P<0.05);compared with IUGR group,the apoptosis rate of pancreatic isletβcells was decreased(P<0.05).(4)Compared with the healthy group,the number of Ngn3 positive cells in pancreatic tissue and Ngn3 protein expression level were decreased in the IUGR group,and the number of Caspase-3 positive cells and Caspase-3 protein expression level

关 键 词：姜黄素 宫内发育迟缓 胰腺发育 糖脂代谢 Ngn3 CASPASE-3 大鼠 

分 类 号：R285.5[医药卫生—中药学]