脂联素对高脂饮食诱导的胰岛素抵抗子宫内膜癌裸鼠移植瘤生长的影响

Effect of adiponectin on the growth of insulin resistance endometrial cancer xenografts in nude mice induced by high-fat diet

目的探讨脂联素对高脂饮食诱导裸鼠胰岛素抵抗子宫内膜癌移植瘤生长的影响。方法 40只裸鼠随机分成高脂组和普食组,每组20只,分别喂养高脂饲料(high-fat diet,HFD)和普通饲料(normal diet,ND),10周后测定裸鼠空腹血糖(fasting blood glucose,FBG)和空腹血胰岛素(fasting serum insulin,FINS)水平,计算胰岛素抵抗指数(HOMA-IR),建立胰岛素抵抗裸鼠模型。第11周接种子宫内膜癌HEC-1B细胞,待瘤体长至0.5 cm时,两组随机选取10只裸鼠腹腔注射脂联素(adiponectin,APN)分为HFD+APN组、ND+APN组;其余裸鼠分别注射0.9%氯化钠分为HFD组、ND组;14周后,测定各组血糖和血脂的代谢情况。结果高脂组裸鼠10周后的平均体重、体长、FBG、FINS、HOMA-IR均大于普食组,糖耐量试验和胰岛素耐量试验结果显示血糖水平亦高于普食组(均P<0.05);接种子宫内膜癌HEC-1B细胞后均成瘤,建模成功。HFD+APN组和ND+APN组移植瘤平均重量和体积增长速度均分别低于HFD组和ND组(均P<0.05)。HFD组和HFD+APN组14周后的FINS、HOMA-IR、TC和TG均较ND组和ND+APN明显升高(均P<0.01),且HFD组明显高于HFD+APN组(均P<0.01);HFD+APN组的血脂联素水平低于ND+APN组(P<0.01),HFD组则低于ND组(P<0.05)。结论脂联素可改善高脂饮食导致的胰岛素抵抗,抑制子宫内膜癌移植瘤生长。

Objective To investigate the effect of adiponectin on the growth of insulin resistance endometrial cancer xenografts in nude mice induced by high-fat diet. Methods Forty nude mice were randomly divided into a high-fat diet group and a normal diet group,with20 rats in each group,which were fed with high-fat diet(HFD) and normal diet(ND),respectively. The levels of fasting blood glucose(FBG)and fasting serum insulin(FINS)in nude mice after feeding 10 weeks were measured,and the insulin resistance index(HOMA-IR)was calculated,resulting in a model of insulin resistance in nude mice. At the 11 th week,endometrial cancer HEC-1B cells were inoculated into nude mice. After the xenografts reached 0.5 cm,10 nude mice were randomly selected from each group,named as HFD+APN group and ND+APN group,respectively,and adiponectin was intraperitoneally injected into nude mice;the remaining nude mice,named HFD group and ND group,respectively,were injected with 0.9% sodium chloride. After 14 weeks,the metabolism of blood glucose and blood lipids in each group was measured. Results The average body weight,body length,FBG,FINS,and HOMA-IR of nude mice in the highfat diet group after feeding 10 weeks were larger than those in the normal diet group,and the results of glucose tolerance test and insulin tol erance test showed that the blood glucose level was also higher than that in the normal diet group(all P<0.05). Nude mice formed tumors after inoculation with endometrial cancer HEC-1B cells,and the modeling was successful. The average weight and volume growth rate of xenografts in the HFD+APN group and the ND+APN group were lower than those in the HFD group and the ND group(all P<0.05). After14 weeks,the level of FINS,HOMA-IR,TC and TG of the HFD group and the HFD+APN group were all higher than those of the ND group and the ND+APN group(all P<0.01),and the HFD group was significantly higher than the HFD+APN group(P<0.01). Serum adiponectin level in the HFD+APN group was significantly lower than that in the ND+APN group(P<0.01),and the HFD group was also significantly lower than the ND group(P<0.05). Conclusion Adiponectin can improve insulin resistance caused by a high-fat diet,inhibiting the growth of endometrial cancer xenografts.