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目的观察大鼠围产期不同时间点(孕20d胎鼠,1、4、10、14日龄鼠)的肺组织MMP2、Ⅳ型胶原表达的变化,并通过对孕鼠注射地塞米松(dexamethasone,DXM),观察其影响。方法24只SD孕大鼠随机分为两组,每组12只。于孕18,19,20d,对照组各肌注0.5ml生理盐水;DXM组肌注DXM0.8mg/(kg.d),取孕20d胎鼠和生后4、10d鼠肺组织,行病理切片,免疫组化染色,计算机图像分析胎鼠和4、10日龄鼠MMP2以及4、10日龄鼠Ⅳ型胶原的分布与表达强度。逆转录聚合酶链反应技术检测肺组织匀浆MMP2mRNA的表达。结果正常4日龄鼠肺囊泡MMP2的表达(20.14±3.39)较胎鼠增强(16.35±2.36),10日龄鼠略下降(15.93±1.94);各日龄DXM组鼠肺MMP2的表达较对照组减少,两者差异有统计学意义(P均<0.01)。DXM组胎鼠、1、4、10日龄鼠肺MMP2mRNA表达均较对照组下调,以4日龄鼠下调最明显(0.376±0.132),胎鼠、1、4日龄鼠比较差异有统计学意义(P均<0.01)。正常4、10日龄鼠肺基底膜的Ⅳ型胶原表达呈不连续线状,间有缺损,量较少,色较浅;DXM组鼠肺基底膜的Ⅳ型胶原表达较多、色较深、呈连续的线状,表达量、阳性强度明显上调。结论孕后期使用地塞米松会抑制新生鼠肺组织的MMP2的表达,使Ⅳ型胶原的降解减少,阻碍基底膜的发育,从而影响肺泡发育。
Objective To observe the changes of MMP2 and type Ⅳ collagen expression in the lung tissue of rats at different time points (20 days gestation, 1, 4, 10, 14 days gestation), and to observe the changes of collagen type Ⅳ expression in dexamethasone , DXM), observe its impact. Methods Twenty-four SD pregnant rats were randomly divided into two groups, 12 rats in each group. On the 18th, 19th and 20th day of gestation, 0.5ml saline was intramuscularly injected into the control group. The DXM group was injected intraperitoneally DXM 0.8mg / (kg · d) Immunohistochemistry and computer image analysis were used to analyze the distribution and expression of type Ⅳ collagen in fetus and 4, 10-day-old rats MMP4 and 4, 10-day-old rats. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect MMP2 mRNA expression in lung homogenate. Results The expression of MMP2 in normal alveolar vesicles in normal 4-day-old mice (20.14 ± 3.39) was significantly higher than that in fetal rats (16.35 ± 2.36) and slightly decreased in 10-day-old rats (15.93 ± 1.94) The control group decreased, the difference was statistically significant (P <0.01). The expression of MMP2mRNA in the lungs of DXM group was lower than that of the control group at the 4th, 10th and the 10th day of gestation, the most significant decrease was in the 4-day-old mice (0.376 ± 0.132), the difference was statistically significant Significance (P <0.01). The expression of type IV collagen in the basement membrane of lung in normal rats on the 4th and 10th day was discontinuous, and there was a small amount of defect between them. The expression of type IV collagen in the basement membrane of DXM group was more , Was a continuous line, the amount of expression, positive intensity was significantly increased. Conclusions Dexamethasone can inhibit the expression of MMP2 in lung tissue of neonatal rats during the second trimester of pregnancy, reduce the degradation of type Ⅳ collagen and hinder the development of basement membrane, thus affecting the alveolar development.