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目的探讨蛋白酪氨酸磷酸酶1 B(PTP 1 B)在空回肠旁路术治疗2型糖尿病(T2DM)大鼠中的作用及其机制。方法采用随机数字表法随机抽取T2DM SD大鼠和正常SD大鼠各24只,并分别随机分为T2DM SD大鼠空回肠旁路术组(DJBO组)和假手术组(DSO组)、正常SD大鼠空回肠旁路术组(NJBO组)和假手术组(NSO组),每组12只。然后测量各组大鼠不同时间点的空腹体重、空腹血糖(FPG)、空腹血清胰岛素(FINS)及稳态模式胰岛素抵抗(HOMA-IR)指数指标,同时应用免疫组织化学染色方法和Western blot法测定各组大鼠骨骼肌中PTP 1 B蛋白的表达情况。结果①造模前,高脂饲料喂养的大鼠空腹体重与普通饲料喂养的大鼠空腹体重比较差异无统计学意义(P>0.05);造模后第4周和第8周时,高脂饲料喂养的大鼠空腹体重明显重于普通饲料喂养的大鼠空腹体重(P<0.05)。②术前,DJBO组和DSO组大鼠的空腹体重、FPG、FINS及HOMA-IR指数均分别明显高于NJBO组(P<0.05)和NSO组(P<0.05),DJBO组与DSO组间和NJBO组与NSO组间以上指标比较差异均无统计学意义(P>0.05)。③术后第4、8周时,DJBO组的空腹体重、FPG、FINS及HOMA-IR指数均明显低于术前(P<0.05);而DSO组和NSO组术后第4、8周时的空腹体重以及NJBO组术后第8周时的空腹体重均明显高于术前(P<0.05),NJBO组术后第4周时空腹体重与术前比较差异无统计学意义(P>0.05),这3组内其余3个指标术后不同时相与术前比较差异均无统计学意义(P>0.05)。④术后第8周时,大鼠骨骼肌中PTP 1 B蛋白表达水平在DSO组明显高于DJBO组(P<0.05)、NSO组(P<0.05)和NJBO组(P<0.05),在DJBO组中明显高于NSO组(P<0.05)和NJBO组(P<0.05),在NSO组和NJBO组间比较差异无统计学意义(P>0.05)。结论空回肠旁路术可能通过减低T2DM大鼠骨骼肌中PTP 1 B的蛋白表达水平,改善胰岛素抵抗,从而有效降低T2DM大鼠血糖水平和空腹体重。
Objective To investigate the role and mechanism of protein tyrosine phosphatase 1 B (PTP 1 B) in type 2 diabetes mellitus (T2DM) rats treated with empty ileum bypass. Methods Twenty-four T2DM SD rats and 24 normal SD rats were randomly selected and randomly divided into T2DM SD rats with empty bowel bypass (DJBO) group and sham operation group (DSO group) SD rats in ileal bypass group (NJBO group) and sham operation group (NSO group), 12 in each group. Fasting weight, fasting blood glucose (FPG), fasting serum insulin (FINS) and homeostasis model insulin resistance index (HOMA-IR) were measured at different time points. Immunohistochemical staining and Western blot The expression of PTP 1 B protein in skeletal muscle of rats in each group was measured. Results ① There was no significant difference in fasting body weight between the rats fed with high fat diet and those fed with normal diet before and after the model diet (P> 0.05). At the 4th week and the 8th week after modeling, The fasting body weight of rats fed with diet was significantly higher than that of the normal diet fed rats (P <0.05). ② Before operation, the body weight, FPG, FINS and HOMA-IR index of rats in DJBO group and DSO group were significantly higher than those in NJBO group and NSO group (P <0.05) There was no significant difference in the above indexes between NJBO group and NSO group (P> 0.05). ③ At 4 and 8 weeks after operation, the fasting weight, FPG, FINS and HOMA-IR index in DJBO group were significantly lower than those in preoperative (P <0.05); while in DSO group and NSO group, (P> 0.05). There was no significant difference in fasting body weight between the NJBO group and the preoperative value at the 4th week after operation (P> 0.05) ). There was no significant difference between the three groups in the postoperative time and before operation (P> 0.05). ④ At 8 weeks after operation, the PTP 1 B protein expression in skeletal muscle of rats in DSO group was significantly higher than that in DJBO group (P <0.05), NSO group (P <0.05) and NJBO group (P <0.05) The DJBO group was significantly higher than the NSO group (P <0.05) and the NJBO group (P <0.05), but there was no significant difference between the NSO group and the NJBO group (P> 0.05). Conclusion Ileum bypass may reduce the level of PTP 1 B protein in skeletal muscle of T2DM rats and improve the insulin resistance, so as to decrease the blood sugar and fasting body weight of T2DM rats.