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目的探讨高氧性肺损伤新生未成熟大鼠肺纤维化过程中Ⅰ、Ⅲ型胶原的沉积情况,并观察N-乙酰半胱氨酸(NAC)的干预效果,以期为临床防治高氧性肺损伤后肺纤维化提供一条新的有效途径。方法将200只孕21d(足月为22~23d)剖宫产出生的新生SD大鼠随机分为空气组(Ⅰ组)、高氧组(Ⅱ组)、高氧+生理盐水(NS)组(Ⅲ组)、高氧+小剂量NAC组(Ⅳ组)、高氧+大剂量NAC组(Ⅴ组)共5个组,每组40只。每组又随机分为3d、7d、14d和21d共4个亚组,每个亚组10只。Ⅰ组在空气中饲养;Ⅱ、Ⅲ、Ⅳ、Ⅴ组置于同一室的高浓度氧(>95%)箱中饲养;Ⅳ、Ⅴ组大鼠以灌胃方式给予NAC(大剂量组每天给予6·25×10-5gNAC/g体重,小剂量组是大剂量的1/4);Ⅲ组给予相同容量的NS。光镜观察各组大鼠肺组织病理形态学;应用图像分析方法检测肺组织Ⅰ、Ⅲ型胶原的含量,并比较各组大鼠肺组织Ⅰ、Ⅲ型胶原含量的差别。结果3、7d时各组大鼠肺组织Ⅰ型胶原免疫组化PU值的差异均无统计学意义(P均>0·05);14、21d时Ⅱ组较Ⅰ组明显增高(P均<0·01),Ⅴ组则较Ⅱ组明显降低(P分别为0·015、0·001)。3d时各组大鼠肺组织Ⅲ型胶原免疫组化PU值的差异无统计学意义(P>0·05);7、14、21dⅡ组较Ⅰ组显著增加(P均<0·01),Ⅴ组则显著低于Ⅱ组(P均<0·01)。对各时间点Ⅳ组与Ⅱ组Ⅰ、Ⅲ型胶原的表达量之间进行比较,差异均无统计学意义(P>0·05)。结论高氧性肺损伤新生未成熟大鼠肺纤维化过程中Ⅰ、Ⅲ型胶原沉积增加,NAC对高氧性肺损伤后肺纤维化具有抑制作用,其作用具有剂量依赖性。
Objective To investigate the deposition of type Ⅰ and type Ⅲ collagen during pulmonary fibrosis in neonatal immature rats with hyperoxia-induced lung injury and to observe the intervention effect of N-acetylcysteine (NAC) for the purpose of clinical prevention and treatment of hyperoxic lung Post-injury pulmonary fibrosis provides a new and effective way. Methods Totally 200 newborn SD rats born from cesarean section during 21 days of pregnancy (full-term 22 ~ 23 days) were randomly divided into two groups: air group (group Ⅰ), hyperoxia group (group Ⅱ), hyperoxia + saline group (Group Ⅲ), hyperoxia + low dose NAC group (group Ⅳ) and hyperoxia + high dose NAC group (groupⅤ). Each group was randomly divided into 3d, 7d, 14d and 21d total 4 subgroups, 10 in each subgroup. Group Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ were housed in a high concentration of oxygen (> 95%) in the same chamber. Rats in groups Ⅳ and Ⅴ were given intragastric administration of NAC 6 · 25 × 10-5gNAC / g body weight, small dose group is a large dose of 1/4); Ⅲ group was given the same volume of NS. The lung histopathology was observed with light microscope. The contents of type I and type III collagen in lung tissue were detected by image analysis. The differences of collagen type I and type III in lung tissue were compared between the two groups. Results At 3 and 7 days, there was no significant difference in the PU value of type Ⅰ collagen between the lungs of rats in each group (all P> 0.05). At 14 and 21 days, the level of PU in group Ⅱ was significantly increased (P < 0 · 01), and group Ⅴ decreased significantly compared with group Ⅱ (P = 0.015,0.0001, respectively). There was no significant difference in the PU value of type Ⅲ collagen between the three groups (P> 0.05) at 3d, and at 7, 14, and 21 d after operation (P <0.01) Group V was significantly lower than Group Ⅱ (P <0.01). There was no significant difference in the expression of type Ⅰ and type Ⅲ collagen between group Ⅳ and group Ⅱ at each time point (P> 0.05). Conclusions The deposition of type Ⅰ and type Ⅲ collagen in pulmonary fibrosis of neonatal immature rats with hyperoxia-induced lung injury increases. NAC can inhibit pulmonary fibrosis in rats with hyperoxia-induced lung injury in a dose-dependent manner.