空回肠旁路术对2型糖尿病大鼠骨骼肌蛋白酪氨酸磷酸酶1B表达的影响

Effect of Jejunoileal Bypass on Protein Tyrosine Phosphatase 1B Protein Expression in Skeletal Muscle of Rats with Type 2 Diabetes Mellitus

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 role and mechanism of protein tyrosine phosphatase 1B （PTP1B） in jejunoi- leal bypass to treating rats with type 2 diabetes mellitus （T2DM）. Methods Twenty-four T2DM SD rats and 24 normal SD rats were selected randomly by using random number table, then the SD rats with T2DM were randomly divided into jejunoileal bypass operation （DJBO, n=12） group and sham operation （DSO, n=12） group, the SD rats with normal food diet were randomly divided into j ejunoileal bypass operation （NJBO, n= 12） group and sham operation （NSO, n= 12） group. Subsequently, fasting body weight （FBW）, fasting plasma glucose （FPG）, fasting insulin （FINS）, and homeostasis model-insulin resistant （HOMA-IR） index of rats in each group were tested at different time points （before operation, on week 4 and 8 after operation）. In addition, expression of PTP1B protein in skeletal muscle was determined by immuno-histochemical staining and Western blot method respectively. Results （1） The FBW before making T2DM model had no significant difference between the rats with high-fat diet and with normal diet （P〉0.05）, which on week 4 or 8 after making T2DM model in the rats with high-fat diet was significantly heavier than that in the rats with normal diet （P〈O.05）. （2） Before jejunoileal bypass operation, the FBW, FPG, FINS, and HOMA-IR index in the DIBO group and the DSO group were significantly higher than those in the NJBO group and the NSO group （P〈0.05）, respectively, which had no significant differe- nces between the DJBO group and the DSO group （P〉0.05） and between the NJBO group and the NSO group （P〉0.05）. （3） Compared with the values before jejunoileal bypass operation, the FBW, FPG, FINS, and HOMA-IR index on week 4 or 8 after jejunoileal bypass operation were significantly decreased in the DIBO group （P〈0.05）; the FBW was significantly increased on week 4 or 8 after jejunoileal bypass operation in the DSO group and the NSO group （P〈0.05）, and on week 8 after jejunoileal bypass operation in the N^BO group （P〈O.05）. The other indexes had no significant differences between before and after jejunoileal bypass operation in the DSO group, the NSO group, or the NJBO group （P〉0.05）. （4） On week 8 after jejunoileal bypass operation, the expression of PTP1B protein in the DSO group was significantly higher than that in the DJBO group, the NSO group or the NJBO group （P〈0.05）, which in the DJBO group was significantly higher than that in the NSO group （P〈0.05） or the NIBO group （P〈O.05）, which had no significant difference between the NIBO group and the NSO group （P〉0.05）. Conclusion Jejunoileal bypass could effectively improve insulin resistance and decrease FPG level and FBW of T2DM rats through inhibiting expression of PTP 1B protein in skeletal muscle of rat with T2DM.