高脂饮食对青春期大鼠的生长发育及胰岛素样生长因子-1、胰岛素受体底物-1的影响

Effects of high - fat feeding on growth and expression of IGF - 1 and IRS - 1 in adolescent rats

目的研究高脂饮食对青春期大鼠生长发育及胰岛素样生长因子-1（IGF-1）、胰岛素受体底物-1（IRS-1）的影响，探讨肝组织中IGF-1、IRS-1与非酒精性脂肪性肝病（NAFLD）大鼠生长落后的关系。方法雄性sD大鼠36只，采用数字表法随机分成正常对照组（NC组，n=18）和高脂组（HF组，n=18），利用高脂饮食建立NAFLD的模型，免疫组化法与RT—PCR检测肝脏IGF—1、IRS-1蛋白和mRNA的表达。结果与NC组比较，HF组8周的血清丙氨酸氨基转移酶（ALT）、总胆固醇（TC）、甘油三酯（TG）在第6、8、12周逐渐升高。HF组8周的血清ALT[（194．67±11．15）U／L]、TC[（1．81±0．09）mmol／L]、TG[（0．34±0．05）mmol／L]的含量均较6周[分别为（166．0±22．01）U／L、（1．52±0．22）mmol／L、（0．41±0．12）mmol／L]升高（均P〈0．05），12周的ALT[（213．00±27．67）U／L]、TC[（2．15±0．37）mmol／L]、TG[（0．38±0．15）mmol／L]较6周和8周均显著增高。高脂组大鼠的体质及体长较NC组生长落后。HF组肝组织病理随时间延长，在6、8、12周肝组织的脂肪变、炎症程度、气球样变逐渐增强。免疫组化显示，HF组IRS-1[（1．46±0．23）、（0．74±0．17）、（0．85±0．31）]、IGF-1[（0．92±0．02）、（0．83±0．02）、（0．77±0．03）]的表达逐渐下降，差异有统计学意义（F=36．024，P〈0．05）。HF组IGF-1和IRS-1的mRNA表达与组化结果-致。结论肝组织IGF·1、IRS-1的表达水平与大鼠的体质与体长呈正相关，青春期高脂饮食会影响大鼠的生长发育，可能与肝组织IGF-1、IRS-1的水平下降有关。

Objective To observe the effects of high - fat feeding on growth and the expression of insulin - like growth factor 1 （ IGF - 1 ） ,insulin receptor suhstrate 1 （ IRS - 1 ） in adolescent rats＇liver with non - alcoholic fatty liver disease, and to elucidate the relationship between growth failure in adolescent rats with non - alcoholic fatty liver disease and IGF - 1, IRS - 1 turbulence. Methods Thirty - six Sprague - Dawley （ SD ） young rats of 21 days were randomly divided into normal control group （NC group, n = 18 ） and high -fat feeding group（ HF group, n = 18 ）. Non - alcoholic fatty liver disease（NAFLD） model was induced by feeding the SD rats with high -fat food. Immunohisto- chemistry was applied to detect the expression levels of IGF - 1 and IRS - 1 in liver tissue. The expressions of mRNA of IGF - 1 and IRS - 1 were measured by RT - PCR. Results Compared with NC group, the serum alanine amino transferase（ALT）, total cholesterol （TC）, triglyeeride （TG） of HF group in the 6th, 8th, 12th week were gradually increased. The serum ALT [ （ 194.67 ± 11.15 ） U/L ], TC [ （ 1.81 ± 0.09 ） mmol/L 1, TG [ （0.34 ± 0.05 ） mmol/L ] contents of HF group at 8th week were higher than those at 6th week [ （ 166.00 ± 22.01 ） U/L, （ 1.52 ± 0.22） mmol/L, （0.41 ±0.12）mmol/L,respectively] ,and the serum ALT[ （213.0±27.67）U/L] ,TC[ （2.15 ±0.37） mmol/L],TG[ （0.38 ± 0.15）mmol/L] contents of the 12th week were significantly increased compared with 6th week and 8th week. The constitution and body length of the HF group were lower than those of the normal control group. With time extended, the liver tissue steatosis,inflammation, the balloon like change of the liver tissue pathology of HF group in 6,8,12th week gradually increased. Immunohistochemistry results showed that HF group IRS - 1 [ （ 1.46 ± 0.23 ）, （0.74 ± 0. 17 ）, （0.85 ± 0.31 ） ], IGF - 1 [ （0.92 ± 0.02）, （0.83 ± 0.02）, （0.77 ± 0.03 ） ] expression gradually decreased, the difference was statistically significant （ F = 36.024, P 〈 0.05 ）. IGF - 1 and IRS - 1 mRNA expressions in HF group were consistent. Conclusion The liver tissue IGF - 1 and IRS - 1 are correlated with the weight and body length. The growth failure of young rats induced by high - fat feeding may be related to the decreased expression of IGF - 1 and IRS - 1.