肥胖的非糖尿病大鼠对急性炎症刺激的耐受性研究

Responsive ability of obese non-diabetic rats to acute inflammatory stimulus

目的比较由高脂膳食诱发肥胖的非糖尿病和2型糖尿病大鼠对急性炎症刺激的反应能力。方法对2型糖尿病GK大鼠(GK组)和Wistar大鼠(Wistar组)进行高脂饲料喂养14周,观察两组大鼠体质量的变化情况。按随机数字表法将高脂饲料喂养14周后的大鼠再分为GK高脂喂养基线组(GK+HFF组)、Wistar+HFF组、GK高脂喂养后内毒素(LPS)注射组(GK+HFF+LPS组)和Wistar+HFF+LPS组,每组6只。取GK+HFF+LPS组和Wistar+HFF+LPS组大鼠,分别以5 mg/kg LPS经腹腔注射建立脓毒血症危重病模型,观察大鼠血糖波动情况,Real-Time PCR检测肝脏、肺脏、肾脏和心肌组织中肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、IL-6和IL-10等炎症细胞因子mRNA的表达。结果高脂喂养14周后,Wistar组大鼠的体质量明显大于GK组(P<0.05),GK组大鼠血糖浓度显著高于Wistar组(P<0.05)。LPS注射后,GK+HFF+LPS组大鼠血糖浓度上升趋势明显,而Wistar+HFF+LPS组大鼠的血糖浓度无明显变化。炎症细胞因子mRNA表达的检测结果显示:Wistar+HFF+LPS组显著高于Wistar+HFF组(P<0.05),GK+HFF+LPS组显著高于GK+HFF组(P<0.05);Wistar+HFF+LPS组炎症细胞因子mRNA表达的上升幅度与GK+HFF+LPS组比较,差异无统计学意义(P>0.05)。结论正常大鼠经高脂膳食诱发肥胖后,对急性炎症刺激出现一定的耐受性,且较2型糖尿病大鼠更为显著。

Objective To investigate the responsive ability to acute inflammatory stimulus of type 2 diabetic rats and obese non-diabetic rats induced by high-fat diet. Methods Type 2 diabetic GK rats （GK group） and Wistar rats （Wistar group） were fed with high-fat diet for 14 weeks, and the body weight of rats in two groups were observed. Then rats were allocated to GK high-fat feeding baseline group （GK ＋ HFF group）, Wistar ＋ HFF group, GK high-fat feeding ＋ lipopolysaccharide （LPS） injection group （GK ＋ HFF ＋ LPS group） and Wistar ＋ HFF ＋ LPS group by random number table, with 6 rats in each group. Severe sepsis model was established by intraperitoneal injection of 5 mg/kg LPS in GK ＋ HFF ＋ LPS group and Wistar ＋ HFF ＋ LPS group. The blood glucose fluctuation was observed, and the expression of tumor necrosis factor-or （TNF- α）, interleukin-1 6 （IL-1 6）, IL-6 and IL-IO mRNA in liver, lung, kidney and myocardial tissues was determined by Real- Time PCR. Results After feeding with high-fat diet for 14 weeks, the body weight of rats in Wistar group was significantly higher than that in GK group （ P 〈 0.05）, and the blood glucose concentration of rats in GK group was significantly higher than that in Wistar group （P 〈 0.05）. After LPS injection, the blood glucose concentration of rats in GK ＋ HFF ＋ LPS group significantly increased, while the blood glucose Concentration of rats in Wistar ＋ HFF ＋ LPS group did not change significantly. Real-Time PCR revealed that the expression of TNF-α, IL-1β, IL-6 and IL-10 mRNA in Wistar ＋ HFF ＋ LPS group was significantly higher than that in Wistar ＋ HFF group （P 〈 0. 05）, and the expression of TNF-α, IL-1β, IL-6 and IL-10 mRNA in GK ＋ HFF ＋ LPS group was significantly higher than that in GK ＋ HFF group （P 〈 0. 05）. The increase of expression of TNF-α, IL-16, IL-6 and IL-10 mRNA in Wistar ＋ HFF ＋ LPS group was not significantly different from that in GK ＋ HFF ＋ LPS group （P 〉 0.05）. Conclusion After feeding with high-fat diet, the tolerance to acute inflammation may increase in obese non-diabetic rats, which is more significant than that in type 2 diabetic rats.