【摘要】 目的 探讨高温加工饲料诱导大鼠非肥胖代谢相关脂肪性肝病的发病机制。方法 实验于2022年1—6月在济南市中心医院实施，72只大鼠根据随机数表法分成4组，分别为正常对照组、未炒黄豆组、炒黄豆组和高脂组，每组18只，于第4、8、12周各解剖6只大鼠。留取大鼠血清、尿液、肝脏用于检测。观察各组大鼠体质量、Lee’s指数、肝重、内脏脂肪、血脂、肝酶水平，检测各组大鼠肝组织反应活性氧水平，检测各组大鼠血清、尿液、肝脏中白三烯E4(cysteine leukotriene E4, CysLTE4)，白三烯B4(cysteine leukotriene B4, CysLTB4)水平；检测各组大鼠血清肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白介素-6(interleukin, IL-6)和晚期糖基化产物（advanced glycation end-product, AGE）水平；检测各组大鼠血糖、血清胰岛素和胰岛素水平及胰岛素抵抗（homeostasis model assessment of insulin resistanc, HOMA-IR）指数。结果 正常对照组与炒黄豆组大鼠在第4周、8周和12周时体质量、Lee’s指数、肝指数和内脏脂肪比较，差异无统计学意义（P均>0.05）。第8周时，炒黄豆组大鼠肝脏ROS表达水平为（2±0.12）μg/mL，显著高于正常对照组（1±0.06）μg/mL、未炒黄豆组（0.8±0.15）μg/mL及高脂组（1.3±0.10）μg/mL，差异有统计学意义（P均<0.001）。第12周时，与正常对照组（1.1±0.09）μg/mL和未炒黄豆组（1.4±0.16）μg/mL相比，炒黄豆组大鼠肝脏ROS表达水平显著升高（2.1±0.08）μg/mL，差异有统计学意义（P均<0.001）。第12周时，炒黄豆组大鼠血清LTB4、LTE4水平分别为（54.11±5.90）、（6.36±0.36）pg/mL，显著高于正常对照组（30.35±3.67）、（3.6±0.62）pg/mL，未炒黄豆组（31.87±5.76）、（4.49±0.64）pg/mL及高脂组（31.04±3.60）、（4.1±0.72）pg/mL，差异有统计学意义（P均<0.05）。第12周时，炒黄豆组大鼠肝脏LTB4、LTE4水平分别为（382.36±68.47）、（63.62±2.23）pg/mL，显著高于正常对照组的（136.87±16.52）、（22.43±2.87）pg/mL，未炒黄豆组的（228.24±62.18）、（36.18±6.50）pg/mL及高脂组的（200.49±10.78）、（21.67±5.82）pg/mL，差异有统计学意义（P均<0.05）。结论 干炒黄豆饲料可能通过增强大鼠体内氧化损伤导致炎症介质LTB4、LTE4水平升高，使大鼠肝脏较早发生纤维化。更多还原

【Abstract】 Objective To investigate the pathogenesis of non-obese metabolism-related fatty liver disease induced by high temperature processed feed in rats. Methods The experiment was carried out in Jinan Central Hospital from January to June 2022. 72 rats were divided into 4 groups by random number table method: normal control group, uncooked soybean group, cooked soybean group and high fat group, with eighteen rats in each group. Six rats were dissected at 4, 8 and 12 weeks. Serum, urine and liver of rats were collected for detection. The body weight, Lee’s index,liver weight, visceral fat, blood lipid and liver enzyme levels of rats in each group were observed, and the reactive oxygen species(ROS) levels of liver tissues were detected. The levels of leukotriene E4(LTE4) and leukotriene B4(LTB4) in serum, urine and liver were detected. Serum levels of TNF-a, IL-6 and advanced glycation end-product(AGE) were determined. Blood glucose, serum insulin, insulin levels and homeostasis model assessment of insulin resistanc(HOMA-IR) index were detected in each group. Results There was no statistically significant difference in body mass, Lee’s index, liver index and visceral fat in the cooked soybean group and the normal control group at week 4, 8 and 12(all P>0.05). At the 8th week, the ROS expression level in the cooked soybean group was(2±0.12) μg/mL,which was significantly higher than that of the normal group(1±0.06) μg/mL, the uncooked soybean group(0.8±0.15) μg/mL and the high fat group(1.3±0.10) μg/mL, the difference was statistically significant(all P<0.001). At week 12, ROS expression levels in the liver in the cooked soybean group were significantly increased(2.1±0.08) μg/mL compared with(1.1±0.09) μg/mL in the normal control group and(1.4±0.16) μg/mL in the uncooked soybean group,and the difference was statistically significant(all P<0.001). At the 12th week, the serum LTB4 and LTE4 levels of 6rats in the cooked soybean group were(54.11±5.90) pg/mL and(6.36±0.36) pg/mL, respectively, they were significantly higher than(30.35±3.67) pg/mL and(3.6±0.62) pg/mL in normal group,(31.87±5.76) pg/mL and(4.49±0.64) pg/mL in uncooked soybean group, and(31.04±3.60) pg/mL and(4.1±0.72) pg/mL in high fat group, the difference was statistically significant(all P<0.05). At the 12th week, the levels of LTB4 and LTE4 in the liver of 6 rats in the cooked soybean group were(382.36±68.47) pg/mL and(63.62±2.23) pg/mL, respectively, they were significantly higher than(136.87±16.52) pg/mL,(22.43±2.87) pg/mL in the normal group,(228.24±62.18) pg/mL,(36.18±6.50) pg/mL in the uncooked soybean group and(200.49±10.78) pg/mL,(21.67±5.82) pg/mL in the high fat group, the difference was statistically significant(all P<0.05). Conclusion Dry cooked soybean diet may increase the levels of inflammatory mediators LTB4 and LTE4 by enhancing oxidative damage in rats, and cause early liver fibrosis in rats.更多还原