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目的观察人脐带间充质干细胞(HUCBMSCs)对肺纤维化小鼠肺组织γ干扰素(IFN-γ)、白细胞介素-4(IL-4)mRNA表达及支气管肺泡灌洗液(BALF)中IFN-γ、IL-4浓度的影响,探讨HUCBMSCs对肺纤维化的干预作用及可能的作用机制。方法 60只雌性小鼠随机分成BLM组、HUCBMSCs组、对照组3组,每组20只。BLM组、HUCBMSCs组分别经气管注入博莱霉素制备肺纤维化模型,对照组经气管注入等体积生理盐水,HUCBMSCs组于造模后6 h经尾静脉注射HUMSCs 200μL。于实验第3、7、14、28天分别随机处死5只小鼠,收集BALF检测其细胞因子IFN-γ、IL-4的浓度;留取肺组织行病理HE染色,测定羟脯氨酸含量,提取肺组织RNA检测IFN-γ、IL-4 mRNA的表达量。结果 (1)肺组织病理:BLM组表现为炎性细胞浸润,肺泡间隔增宽;HUCBMSCs组肺泡炎及肺间质纤维化较BLM组明显减轻。(2)与对照组比较,BLM组和HUCBMSCs组肺系数均明显升高(P<0.05);而HUCBMSCs组第14、28天较BLM组明显下降(P<0.05)。(3)BLM组和HUCBMSCs组第14、28天羟脯氨酸的含量均较对照组明显升高(P<0.05),而HUCBMSCs组较BLM组则明显降低(P<0.05)。(4)与对照组比较,BLM组IFN-γmRNA表达量、IFN-γ浓度明显降低(P<0.05),而IL-4 mRNA表达量、IL-4浓度明显升高(P<0.05);与BLM组比较,HUCBMSCs组IFN-γmRNA表达量、IFN-γ浓度明显升高(P<0.05),而IL-4 mRNA表达量、IL-4浓度则明显降低(P<0.05);且BLM组和HUCBMSCs组IL-4与IFN-γ均呈负相关(P<0.05)。结论 HUCBMSCs对肺纤维化有较好的治疗作用,其机制可能是通过逆转Th1/Th2细胞因子的失衡实现的,且通过对BALF中IFN-γ、IL-4浓度的检测可能对肺纤维化的严重程度的判断有一定的临床意义。
Objective To observe the effect of human umbilical cord mesenchymal stem cells (HUCBMSCs) on the expression of IFN-γ and IL-4 in bronchoalveolar lavage fluid (BALF) IFN-γ, IL-4 concentration, to explore the intervention of HUCBMSCs on pulmonary fibrosis and its possible mechanism. Methods Sixty female mice were randomly divided into BLM group, HUCBMSCs group and control group with 20 rats in each group. In BLM group and HUCBMSCs group, bleomycin was injected intratracheally into pulmonary fibrosis model. In the control group, an equal volume of normal saline was injected into the control group. HUCBMSCs group was injected with 200 μL of HUMSCs through tail vein at 6 h after modeling. On the 3rd, 7th, 14th and 28th day of the experiment, 5 mice were randomly sacrificed and the concentrations of IFN-γ and IL-4 in BALF were measured. The lung tissues were collected for histopathological HE staining and hydroxyproline content , And lung tissue RNA was extracted to detect the expression of IFN-γ and IL-4 mRNA. Results (1) Pathology of lung: BLM showed inflammatory cell infiltration with widened alveolar septum. Alveolitis and interstitial fibrosis in HUCBMSCs group were significantly reduced compared with BLM group. (2) Compared with the control group, the lung coefficient of BLM group and HUCBMSCs group were significantly increased (P <0.05), while HUCBMSCs group was significantly lower than the BLM group on the 14th and 28th days (P <0.05). (3) The contents of hydroxyproline in BLM group and HUCBMSCs group on the 14th and 28th day were significantly higher than those in the control group (P <0.05), while those in the HUCBMSCs group were significantly lower than those on the BLM group (P <0.05). (4) Compared with the control group, the expression of IFN-γmRNA and the concentration of IFN-γ in BLM group were significantly decreased (P <0.05), while the expression of IL-4 mRNA and IL-4 in BLM group were significantly increased Compared with BLM group, the expression of IFN-γ mRNA and the concentration of IFN-γ in HUCBMSCs were significantly increased (P <0.05), while the expression of IL-4 mRNA and IL-4 in HMBBMSCs were significantly decreased There was a negative correlation between IL-4 and IFN-γ in HUCBMSCs (P <0.05). Conclusions HUCBMSCs have a good therapeutic effect on pulmonary fibrosis. The mechanism may be through reversing the imbalance of Th1 / Th2 cytokines, and the detection of IFN-γ and IL-4 in BALF may play an important role in the pathogenesis of pulmonary fibrosis Severity of judgment has some clinical significance.