生长激素对运动大鼠胰岛β细胞形态和功能影响的研究
摘要
目的：本研究以大鼠为实验对象，注射重组人生长激素(rhGH)，结合耐力运动训练，观察rhGH对血糖、血清胰岛素、血清C肽、肝糖原和肌糖原等指标的影响，并结合胰岛β细胞形态的变化，探讨使用外源性生长激素诱发继发性糖尿病的可能性及其机制，为反兴奋剂教育提供科学理论依据。
研究方法：28只雄性成年SD大鼠(7周龄)，随机分为4组：安静对照组(8只)、安静注射组(6只)、单纯运动组(8只)和运动注射组(6只)。运动组和运动注射组先进行适应性训练1周，然后进行正式跑台训练，坡度为上坡5°，速度为20米／分，每日训练1次，每次1小时，每周训练6天。训练4周后，安静注射组和运动注射组给予4周的rhGH皮下注射，剂量为2.5-3mg／kg／d。同时，运动组和运动注射组继续进行跑台训练4周，训练方式与前4周相同。最后一次训练后，禁食12小时于次日晨各组大鼠用2％的戊巴比妥钠腹腔麻醉，断头取血，在胰脏(主要是胰岛集中的胰尾1／3处)、肝脏和腓肠肌部位取样。测试血清胰岛素、C肽，血糖、肌糖原和肝糖原等指标，并用图像分析方法观察胰腺β细胞形态。
结果：1．运动组的血糖值均明显低于安静组(p＜0.01)；而注射组与之相对应的非注射对照组相比，血糖值无显著性差异。2．注射组与之相对应的非注射对照组相比，C肽显著升高(p＜0.05)。3．安静注射组的胰岛素水平明显高于安静对照组；运动注射组的胰岛素与单纯运动组相比，有升高的趋势。4．C肽与空腹血糖的比值(C／G)，运动组均明显高于安静组(p＜0.001)。5．HBCI(β细胞分泌功能指数)，运动注射组比单纯运动组有明显升高(p＜0.05)；安静注射组与安静对照组相比，也有升高趋势。6．注射组与之相对应的非注射对照组相比，肝糖原有降低的趋势；运动组与之相对应的安静对照组相比，肝糖原也有降低的趋势。7．安静对照组的肌糖原明显低于其它3组(p＜0.001)。8．β细胞占胰岛的面积比例，注射组与之相对应的非注射对照组相比，有升高的趋势；但各组之间无显著性差异。
结论：1．rhGH的应用使运动及安静大鼠的血液中胰岛素、C肽浓度升高，而血糖无明显变化，说明rhGH已诱导大鼠产生了胰岛素抵抗。2．C／G及HBCI的结果表明，rhGH可促进β细胞的胰岛素分泌。本实验注射时间仅为4周，推测如果长时间应用rhGH，由于胰岛素抵抗的存在，当β细胞的高胰岛素分泌不能代偿胰岛素抵抗时，可能造成β细胞衰竭，产生继发性糖尿病。3．胰岛β细胞形态学图像分析结果显示注射组β细胞占胰岛面积百分比有增高趋势，从形态学方面说明应用rhGH促进β细胞的胰岛素分泌。
Objective The present study investigated the possibility and mechanism of the secondary diabetes induced by long time rhGH administration.in training rats. Finding ways to provide theoretical basis for anti-drug education. The indexes we monitored include the density of the blood sugar, serum insulin, serum C-peptide, liver glycogen and muscle glycogen, the morphology of B cells et al.
Methods 28 male mature SD rats were randomly divided into 4 groups: i.e. rest group(n=8) , injection group(n=6), exercise group(n=8), exercise plus injection group(n=6). After accustomed for one week; the exercise control group and exercise plus injection group were trained for 8 weeks (grade of 5, at the speed of 20m/min, duration of 1 hour, 6 day/week). Injection protocol: The groups with rhGH-injection were administered with rhGH subcutaneously at 8 p.m. everyday for 4 weeks, (dose: 2.5-3.0mg/kg/d) The resting and exercise control groups were injected the same dose of placebo . Sample collection and measurements were performed after the last injection and a 12-hour fast. The sample we collected includes blood, pancreas, liver and gastrocnemiuses.
Results 1 .The blood sugar of the endurance training group rats are significantly lower than that of the rest control group (P<0.001) ,but there is no significant difference between the injection and the non-injection groups. 2. C-peptides increase significantly in the injection groups compared with the non-injection groups. 3. The serum insulin level of the rest injection group is much higher than that of the resting control group ; the level of the exercise plus injection group is much higher than the exercise group ,but the value failed to reach the significant level. 4. C/G of the exercise groups is significantly higher than that of the rest groups. 5. Compared with HBCI, the level of the exercise plus injection group increased more than that of the exercise group; the levels of the rest injection group increased 6. The liver glycogen of the injected groups is lower than the non-injected groups; the level of the exercise control group dropped also. 7. The muscle glycogen of the resting control group is l
ower than that of the others. 8. The ratio of the areas of p-cell to the pancreatic islets of the injection groups had the trend of increase, but no significant difference observed.
Conclusion 1. The result of the increased serum insulin and C-peptide and their unchanged blood sugar of the rhGH administration groups indicate that rhGH can induce insulin resistance. 2. The result of C/G and HBCI showed that rhGH can stimulate insulin secretion.The duration of injection in this study were only 4 weeks. If rhGH were administrated for a longer time, the function of p-cells would be exhausted and induced the secondary diabetes when the higher insulin secretion could not compensate insulin resistance. 3. The result of P-cells' image analysis showed that the percentage of the ratio of the areas of P-cells to the pancreatic islets had the trend of increase, which further illustrated that the administration of rhGH stimulate insulin secretion by p-cell from morphology .
研究方法：28只雄性成年SD大鼠(7周龄)，随机分为4组：安静对照组(8只)、安静注射组(6只)、单纯运动组(8只)和运动注射组(6只)。运动组和运动注射组先进行适应性训练1周，然后进行正式跑台训练，坡度为上坡5°，速度为20米／分，每日训练1次，每次1小时，每周训练6天。训练4周后，安静注射组和运动注射组给予4周的rhGH皮下注射，剂量为2.5-3mg／kg／d。同时，运动组和运动注射组继续进行跑台训练4周，训练方式与前4周相同。最后一次训练后，禁食12小时于次日晨各组大鼠用2％的戊巴比妥钠腹腔麻醉，断头取血，在胰脏(主要是胰岛集中的胰尾1／3处)、肝脏和腓肠肌部位取样。测试血清胰岛素、C肽，血糖、肌糖原和肝糖原等指标，并用图像分析方法观察胰腺β细胞形态。
结果：1．运动组的血糖值均明显低于安静组(p＜0.01)；而注射组与之相对应的非注射对照组相比，血糖值无显著性差异。2．注射组与之相对应的非注射对照组相比，C肽显著升高(p＜0.05)。3．安静注射组的胰岛素水平明显高于安静对照组；运动注射组的胰岛素与单纯运动组相比，有升高的趋势。4．C肽与空腹血糖的比值(C／G)，运动组均明显高于安静组(p＜0.001)。5．HBCI(β细胞分泌功能指数)，运动注射组比单纯运动组有明显升高(p＜0.05)；安静注射组与安静对照组相比，也有升高趋势。6．注射组与之相对应的非注射对照组相比，肝糖原有降低的趋势；运动组与之相对应的安静对照组相比，肝糖原也有降低的趋势。7．安静对照组的肌糖原明显低于其它3组(p＜0.001)。8．β细胞占胰岛的面积比例，注射组与之相对应的非注射对照组相比，有升高的趋势；但各组之间无显著性差异。
结论：1．rhGH的应用使运动及安静大鼠的血液中胰岛素、C肽浓度升高，而血糖无明显变化，说明rhGH已诱导大鼠产生了胰岛素抵抗。2．C／G及HBCI的结果表明，rhGH可促进β细胞的胰岛素分泌。本实验注射时间仅为4周，推测如果长时间应用rhGH，由于胰岛素抵抗的存在，当β细胞的高胰岛素分泌不能代偿胰岛素抵抗时，可能造成β细胞衰竭，产生继发性糖尿病。3．胰岛β细胞形态学图像分析结果显示注射组β细胞占胰岛面积百分比有增高趋势，从形态学方面说明应用rhGH促进β细胞的胰岛素分泌。
Objective The present study investigated the possibility and mechanism of the secondary diabetes induced by long time rhGH administration.in training rats. Finding ways to provide theoretical basis for anti-drug education. The indexes we monitored include the density of the blood sugar, serum insulin, serum C-peptide, liver glycogen and muscle glycogen, the morphology of B cells et al.
Methods 28 male mature SD rats were randomly divided into 4 groups: i.e. rest group(n=8) , injection group(n=6), exercise group(n=8), exercise plus injection group(n=6). After accustomed for one week; the exercise control group and exercise plus injection group were trained for 8 weeks (grade of 5, at the speed of 20m/min, duration of 1 hour, 6 day/week). Injection protocol: The groups with rhGH-injection were administered with rhGH subcutaneously at 8 p.m. everyday for 4 weeks, (dose: 2.5-3.0mg/kg/d) The resting and exercise control groups were injected the same dose of placebo . Sample collection and measurements were performed after the last injection and a 12-hour fast. The sample we collected includes blood, pancreas, liver and gastrocnemiuses.
Results 1 .The blood sugar of the endurance training group rats are significantly lower than that of the rest control group (P<0.001) ,but there is no significant difference between the injection and the non-injection groups. 2. C-peptides increase significantly in the injection groups compared with the non-injection groups. 3. The serum insulin level of the rest injection group is much higher than that of the resting control group ; the level of the exercise plus injection group is much higher than the exercise group ,but the value failed to reach the significant level. 4. C/G of the exercise groups is significantly higher than that of the rest groups. 5. Compared with HBCI, the level of the exercise plus injection group increased more than that of the exercise group; the levels of the rest injection group increased 6. The liver glycogen of the injected groups is lower than the non-injected groups; the level of the exercise control group dropped also. 7. The muscle glycogen of the resting control group is l
ower than that of the others. 8. The ratio of the areas of p-cell to the pancreatic islets of the injection groups had the trend of increase, but no significant difference observed.
Conclusion 1. The result of the increased serum insulin and C-peptide and their unchanged blood sugar of the rhGH administration groups indicate that rhGH can induce insulin resistance. 2. The result of C/G and HBCI showed that rhGH can stimulate insulin secretion.The duration of injection in this study were only 4 weeks. If rhGH were administrated for a longer time, the function of p-cells would be exhausted and induced the secondary diabetes when the higher insulin secretion could not compensate insulin resistance. 3. The result of P-cells' image analysis showed that the percentage of the ratio of the areas of P-cells to the pancreatic islets had the trend of increase, which further illustrated that the administration of rhGH stimulate insulin secretion by p-cell from morphology .
引文
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