妊娠期糖尿病对肺发育的影响

The Establishment of Gestational Diabetes and Its Effects on Lung Development

目的建立胎儿宫内高血糖暴露模型,探讨该模型对新生鼠不成熟肺细胞凋亡、增殖及肺结构发育的影响。方法健康SD妊娠大鼠随机分成高血糖组(STZ组)和正常妊娠组,每组20只。STZ组:妊娠4.5 d腹腔注射1%链脲佐菌素(STZ)溶液40 mg/kg,正常妊娠组则在相同时点相同条件下注射同体积柠檬酸缓冲液。记录腹腔注射STZ前,妊娠6.5 d、11.5 d、16.5 d和20.5 d两组孕鼠尾静脉随机血糖;记录新生鼠出生当天(D0)、第7天(D7)的体质量、存活率;测量新生鼠D0、D7肺质量、肺间隔厚度、辐射状肺泡计数、肺细胞凋亡和增殖情况。结果注射STZ后,与正常妊娠组相比,STZ组孕鼠各时点随机血糖值显著增高(P<0.05);D0、D7新生鼠存活率降低(P=0.00);D0时新生鼠体质量降低(P<0.05)、相对肺质量降低(P<0.05)、肺间隔变薄(P<0.05),辐射状肺泡计数无明显变化。D0时STZ组肺细胞凋亡指数显著高于正常妊娠组[(11.8±1.1)%比(3.4±0.7)%,P=0.00]。STZ组新生鼠肺细胞增殖在D0、D7均显著增加(P<0.05)。结论妊娠4.5 d腹腔注射1%STZ溶液40 mg/kg,可成功建立胎鼠宫内高血糖暴露模型。胎鼠高血糖暴露可增加出生当天新生鼠死亡率、肺泡细胞凋亡和增殖,影响肺结构的发育。

Objective To establish a model of fetal hyperglycemia and explore the effects of hyperglycemia on alveolar cell apoptosis,proliferation and the development of lung structure in neonatal rats.Methods Forty SD pregnant rats were randomly divided into a hyperglycemia group( STZ group) and a normal pregnancy group( N group)( n = 20 in each group). The rats in STZ group and N group were intraperitoneally injected streptozotocin( STZ,40 mg / kg) or the same bulk of citrate buffer respectively at the4. 5 days after gestation. Blood glucose concentration of the pregnant rats was measured before injection,at the 6. 5,11. 5,16. 5 and 20. 5 days after gestation,respectively. The weight,survival rate,lung weight,septal thickness,radical alveolar count,alveolar cell apoptosis and proliferation of neonatal rats were recorded after birth immediately( D0) and at 7 days( D7). Results Compared with N group,the blood glucose level increased after intraperitoneal injection of STZ in STZ group( P < 0. 05). The Survival rate of STZ group was lower than that of N group at D0 and D7( P = 0. 00). The neonatal weight,lung weight,septal thickness of STZ group were lower compared with those of N group at D0( P < 0. 05). However,there was no significant difference between two groups in radical alveolar count. The alveolar apoptosis index of STZ group was higher than that of N group at D0 [( 11. 8 ± 1. 1) % vs.( 3. 4 ± 0. 7) %,P = 0. 00]. Alveolar cell proliferation significantly increased in STZ group compared with N group at D0 and D7( P < 0. 05). Conclusions The fetal hyperglycemia model is successfully established by intraperitoneal injection of STZ 40 mg / kg. Fetal hyperglycemia can increase mortality,alveolar cell proliferation and apoptosis,and affect the development of lung structure of neonatal rats.