糖尿病基础研究

　　【摘要】目的 检测甲状腺毒症妊娠大鼠胰腺中葡萄糖转运蛋白2(GLUT2)和蛋白酪氨酸磷酸酶-1B(PTP-1B)的表达，探讨其影响糖代谢的可能机制。 方法 雌性SD大鼠分为非妊娠组和待妊娠组，待妊娠组按雌雄比例2:1合笼受孕后进一步分为单纯妊娠(R)组、妊娠期左甲状腺素钠低剂量(RA)组，妊娠期左甲状腺素钠中剂量(RB)组，妊娠期左甲状腺素钠高剂量(RC)组，非妊娠组进一步分为正常对照(N)组，左甲状腺素钠低剂量(A)组，左甲状腺素钠中剂量(B)组，左甲状腺素钠高剂量(C)组。予A、RA组[LT4 50 μg/(100 g·d)]、B、RB组[LT4 100 μg/(100 g·d)]、C、RC组[LT4 150 μg/(100 g·d)]灌胃制造甲状腺毒症模型，N、R组予等量生理盐水。检测各组母鼠甲状腺功能、FPG和FIns，Western blot检测胰腺中GLUT2和PTP-1B的表达。 结果 随着左甲状腺素钠剂量增加，N、A、B、C组和R、RA、RB、RC组游离三碘甲状腺原氨酸(FT3)[(2.65±0.07) vs (4.05±0.10) vs (4.87±0.63) vs (5.62±0.73)pmol/L;(2.67±0.10) vs (4.07±0.09) vs (4.84±0.11) vs (5.65±0.18)pmol/L，P<0.01]、游离甲状腺素(FT4)[(10.54±0.58) vs (13.46±0.78) vs (25.77±0.85) vs (36.58±0.91)pmol/L;(10.61±0.79) vs (13.53±0.66) vs (25.90±1.12) vs (36.65±0.62)pmol/L，P<0.01]升高，促甲状腺激素(TSH)[(0.086±0.009) vs (0.029±0.002) vs (0.024±0.001) vs (0.018±0.002)μU/ml;(0.070±0.009) vs (0.027±0.002) vs (0.021±0.001) vs (0.015±0.002)μU/ml，P<0.01]降低。甲状腺毒症各组(A、B、C组和RA、RB、RC组)FPG较对照组(N组和R组)升高[(5.43±0.32)、(5.74±0.21)、(6.34±0.46) vs (4.98±0.25)mmol/L;(5.37±0.48)、(5.78±0.39)、(6.45±0.44) vs (4.88±0.38)mmol/L，P<0.01]，C组FIns较N组升高[(10.40±1.52) vs (8.25±0.80)μU/ml，P<0.01]，妊娠各组(R、RA、RB、RC组)FIns较非妊娠各组(N、A、B、C组)升高[(9.16±1.28) vs (8.25±0.80)μU/ml;(10.40±1.31) vs (9.20±1.32)μU/ml;(10.41±1.43) vs (9.75±1.24)μU/ml;(11.09±1.17) vs (10.40±1.52)μU/ml，P<0.01]。Western blot结果显示，甲状腺毒症各组GLUT2表达较N、R组降低，PTP-1B表达升高(P<0.05)。 结论 GLUT2及PTP-1B可能与妊娠期合并甲状腺毒症母鼠出现糖代谢异常相关。

　　【关键词】甲状腺毒症;妊娠;胰腺;葡萄糖转运蛋白2;蛋白酪氨酸磷酸酶1B

　　【Abstract】 Objective To investigate the expression of glucose transporter 2 (GLUT2) and protein tyrosine phosphatase-1B (PTP-1B) in pancreas of pregnancy rats with thyrotoxicosis, and to explore the possible mechanism of its effect on glucose metabolism. Methods The female SD rats were randomly divided into non-pregnant group and to be pregnant group. To be pregnant rats were co-caged by the ratio 2:1 of male and female. The pregnancy rats were randomly divided into simple pregnancy (R) group, with low dose of levothyroxine sodium (LT4) (RA) group, with middle dose LT4 (RB) group, and with high dose LT4 (RC) group. The non-pregnant groups were randomly divided into normal control (N) group, low dose LT4 (A) group, middle dose LT4 (B), and high dose LT4 (C) group. The rats were given LT4 in A and RA group [50 μg/(kg·d)], B and RB group [100 μg/(kg·d)], C and RC group [150 μg/(kg·d)] to build hyperthyroidism model. The rats in normal control group and simple pregnancy group were given the same amount of saline. Thyroid function, FPG and Fins were measured in each group. The expressions of GLUT2 and PTP-1B in pancreatic tissue were examined by western blot. Results With the increase in the dose of LT4, the levels of FT3 [(2.65±0.07) vs (4.05±0.10) vs (4.87±0.63) vs (5.62±0.73)pmol/L;(2.67±0.10) vs (4.07±0.09) vs (4.84±0.11) vs (5.65±0.18)pmol/L，P<0.01], FT4 [(10.54±0.58) vs (13.46±0.78) vs (25.77±0.85) vs (36.58±0.91)pmol/L;(10.61±0.79) vs (13.53±0.66) vs (25.90±1.12) vs (36.65±0.62)pmol/L，P<0.01] increased, but the levels of TSH declined [(0.086±0.009) vs (0.029±0.002) vs (0.024±0.001) vs (0.018±0.002)μU/ml;(0.070±0.009) vs (0.027±0.002) vs (0.021±0.001) vs (0.015±0.002)μU/ml，P<0.01]. The levels of FPG in hyperthyroidism groups were significantly higher than N group [(5.43±0.32),(5.74±0.21),(6.34±0.46) vs (4.98±0.25)mmol/L;(5.37±0.48),(5.78±0.39),(6.45±0.44) vs (4.88±0.38)mmol/L, P<0.01]. The level of FIns in severe hyperthyroidism group increased significantly than N group [(10.40±1.52) vs (8.25±0.80)μU/ml, P<0.01] . The level of FIns was higher in pregnant group than in non-pregnant group [(9.16±1.28) vs (8.25±0.80)μU/ml;(10.40±1.31) vs (9.20±1.32)μU/ml;(10.41±1.43) vs (9.75±1.24)μU/ml;(11.09±1.17) vs (10.40±1.52)μU/ml，P<0.01]. Western blot showed GLUT2 protein expressions were lower in three hyperthyroidism groups than in N group. PTP-1B protein expression were higher in hyperthyroidism groups than in N group (P<0.05). Conclusion GLUT2 and PTP-1B may be associated with abnormal glucose metabolism in pregnancy rats with thyrotoxicosis

　　【Key words】 Thyrotoxicosis;Pregnancy;Pancreas;Glucose transporter 2 (GLUT2);Protein tyrosine phosphatase-1B (PTP-1B)