细胞凋亡在重症急性胰腺炎并发急性肺损伤中的作用机制

发布时间：2018-03-21 00:51

本文选题：细胞凋亡　切入点：重症急性胰腺炎　出处：《解放军医学杂志》2017年11期 　论文类型：期刊论文

【摘要】：目的探讨细胞凋亡在重症急性胰腺炎(SAP)并发急性肺损伤(ALI)中的作用,并从Notch/Hes信号转导方面探讨其作用机制。方法 50只健康雄性SD大鼠随机分为假手术组(n=8)和模型组(n=42),模型组采用胰胆管逆行注射3.5%牛磺胆酸钠的方法建立SAP并发ALI模型,并随机分为模型3h组(n=10)、模型6h组(n=10)、模型12h组(n=10)和模型24h组(n=12)。计算肺组织湿/干重比值(W/D),光镜下进行胰腺和肺组织病理评分,酶化学法测定肺组织髓过氧化物酶(MPO)活性,放射免疫分析法测定肺组织肿瘤坏死因子α(TNF-α)水平,TUNEL法检测肺组织细胞凋亡并计算凋亡指数(AI),Western blotting方法测定Notch-1、Hes-1和Hes-5蛋白的表达水平。结果模型大鼠的肺组织W/D呈现逐级增高趋势,各组均明显高于假手术组(P0.01),其中模型12h组达到峰值;各模型组胰腺病理评分和肺组织病理评分均较假手术组明显提高(P0.01),模型12h组最高;各模型组肺组织MPO和TNF-α水平改变与肺组织病理评分呈现相同趋势;各模型组大鼠肺组织细胞凋亡指数(AI)均较假手术组明显增高(P0.01)。Western blotting检测结果提示,4个模型组Notch-1蛋白表达水平均较假手术组下降,其中模型3h、模型6h和模型12h三组与假手术组比较差异有统计学意义(P0.05),模型12h组Notch-1蛋白表达水平最低,明显低于模型3h组、模型6h组和模型24h组(P0.01)。相关性分析显示,肺组织AI与肺损伤病理评分呈显著负相关(r= 0.834,P0.01);模型Notch-1蛋白表达水平与肺组织AI呈显著正相关(r=0.515,P=0.004),与肺组织W/D(r= 0.593,P=0.001)、肺组织病理评分(r= 0.306,P=0.002)、MPO活性(r= 0.687,P0.01)及TNF-α水平(r= 0.574,P=0.001)呈显著负相关。结论 SAP并发ALI过程中,肺组织细胞凋亡增加对减轻肺损伤起重要作用,SAP时Notch-1信号表达受限是肺损伤恶化的重要机制。
[Abstract]:Objective to investigate the role of apoptosis in acute lung injury (Ali) in patients with severe acute pancreatitis (SAP). Methods 50 healthy male Sprague-Dawley rats were randomly divided into sham-operated group and model group. The model group was treated with retrograde injection of 3.5% sodium taurocholate into the pancreatic duct to establish ALI model. The rats were randomly divided into 3 h group, 6 h group, 12 h group, 12 h group and 24 h group, respectively. The wet / dry weight ratio of lung tissue was calculated, the pathological score of pancreas and lung tissue was evaluated under light microscope, and the activity of myeloperoxidase (MPO) in lung tissue was determined by enzyme chemistry. The level of TNF- 伪 TNF- 伪 in lung tissue was measured by radioimmunoassay and Tunel method was used to detect the apoptosis of lung tissue. The expression of Notch-1Hes-1 and Hes-5 protein was measured by Western blotting method. All the groups were significantly higher than the sham-operated group (P 0.01), the model group reached the peak value at 12 h, the pancreatic pathological score and the lung tissue pathological score of each model group were significantly higher than those of the sham operation group, and the model 12h group had the highest value. The changes of MPO and TNF- 伪 in each model group showed the same trend as the pathological score of lung tissue. The expression of Notch-1 protein in the four model groups was significantly lower than that in the sham-operated group. The results showed that the expression of Notch-1 protein in the four model groups was significantly lower than that in the sham operation group. The expression of Notch-1 protein in the model group was the lowest, which was significantly lower than that in the model group at 3 h, 6 h and 12 h. The correlation analysis showed that the expression of Notch-1 protein in the model group was significantly lower than that in the model group at 3 h, 6 h and 12 h. The correlation analysis showed that the expression of Notch-1 protein in the model group was significantly lower than that in the model group at 3 h, 6 h and 12 h, respectively. There was a significant negative correlation between lung tissue AI and lung injury pathological score (r = 0.834 P0.01a), and a positive correlation between the expression of Notch-1 protein and lung tissue AI, a negative correlation between the expression of Notch-1 protein and lung tissue AI, and a negative correlation between the expression level of Notch-1 protein and lung tissue WR / Dnr = 0.593P ~ (0. 001), lung pathological score r = 0. 306P0. 002P0. 01) and TNF- 伪 level (r = 0. 574P = 0. 001). Conclusion in the process of SAP complicated with ALI, The increase of apoptosis in lung tissue plays an important role in alleviating lung injury. The limited expression of Notch-1 signal is an important mechanism of the deterioration of lung injury.
【作者单位】：浙江省中西医结合医院重症医学科;
【基金】：浙江省自然科学基金(LY13H290008) 浙江省医药卫生科技计划项目(2011KYB075)~~
【分类号】：R563.8;R576

【相似文献】