橙皮苷对重症肺炎大鼠肺组织炎症和细胞凋亡影响

Effect of hesperidin on inflammation and apoptosis of lung tissue in rats with severe pneumonia

目的:研究橙皮苷对重症肺炎大鼠肺组织炎症和细胞凋亡影响。方法:构建重症肺炎大鼠模型,分为SD组、Control组、Model组(肺炎模型)、Hesperidin-L组(12 mg/kg橙皮苷治疗)、Hesperidin-M组(24 mg/kg橙皮苷治疗)、Hesperidin-H组(36 mg/kg橙皮苷治疗),检测肺组织湿干重比(W/D),对肺组织病理损伤程度评分,计数肺泡灌洗液中炎症细胞数目,qRTPCR检测肺组织中TNF-α、IL-1β、IL-6、iNOS mRNA水平,ELISA检测TNF-α、IL-1β、IL-6含量,Western blot检测肺组织中Bax、ccaspase-3、Bcl-2、p-STAT3、p-JAK2、STAT3、JAK2、JAK1和p-JAK1蛋白表达水平,TUENL染色检测肺组织中细胞凋亡水平。结果:与Control组相比,Model组大鼠肺组织病理评分升高,W/D升高,肺泡灌洗液中单核巨噬细胞、淋巴细胞、中性粒细胞、白细胞数目均升高,肺组织中炎症介质TNF-α、IL-1β、IL-6、iNOS mRNA表达水平和TNF-α、IL-1β、IL-6含量均升高,肺组织中细胞凋亡水平升高,Bax、c-caspase-3、p-STAT3/STAT3、p-JAK2/JAK2和p-JAK1/JAK1蛋白表达水平升高,Bcl-2蛋白表达水平降低,差异有统计学意义(P<0.05)。与模型组相比,Hesperidin-L、Hesperidin-M、Hesperidin-H组大鼠肺组织病理评分降低,W/D降低,肺泡灌洗液中单核巨噬细胞、淋巴细胞、中性粒细胞、白细胞数目均逐渐减少,肺组织中炎症介质TNF-α、IL-1β、IL-6、iNOS mRNA表达水平和TNF-α、IL-1β、IL-6含量均逐渐降低,细胞凋亡水平逐渐降低,Bax、c-caspase-3、p-STAT3/STAT3、p-JAK2/JAK2和p-JAK1/JAK1蛋白表达水平逐渐降低,Bcl-2蛋白表达水平逐渐升高,差异有统计学意义(P<0.05)。结论:橙皮苷可改善重症肺炎大鼠肺组织炎症,减少细胞凋亡。

Objective:To study the effects of hesperidin on lung inflammation and cell apoptosis in rats with severe pneumonia.Methods:Rats models of severe pneumonia were constructed and divided into SD group,Control group,Model group(pneumonia mod‐el),Hesperidin-L group(12 mg/kg hesperidin treatment),Hesperidin-M group(24 mg/kg hesperidin treatment),Hesperidin-H group(36 mg/kg hesperidin treatment),detected wet-to-dry mass ratio(W/D)of lung tissue,scored degree of lung tissue pathological damage,counted the number of inflammatory cells in alveolar lavage fluid,and detected TNF-α,IL-1β,IL-6,iNOS mRNA levels in lung tissue by qRT-PCR method,ELISA was used to detect contents of TNF-α,IL-1β,IL-6,Western blot was used to detect Bax,c-caspase-3,Bcl-2,p-STAT3,p-JAK2,STAT3,JAK2 and p-JAK1 protein expression levels in lung tissue,TUENL staining was used to detect level of apoptosis in lung tissue.Results:Compared with Control group,lung tissue pathological score of Model group was increased,W/D was increased,the number of mononuclear macrophages,lymphocytes,neutrophils and white blood cells in alveolar lavage fluid were increased,inflammatory mediators TNF-α,IL-1β,IL-6,iNOS mRNA expression levels in lung tissue were increased,so as the contents of TNF-α,IL-1βand IL-6,level of apoptosis in lung tissue was increased,Bax,c-caspase-3,p-STAT3/STAT3,p-JAK2/JAK2 and p-JAK1/JAK1 protein expression levels were increased,while Bcl-2 protein expression level was decreased,the difference was statistically significant(P<0.05).Compared with Model group,rats in Hesperidin-L,Hesperidin-M and Hesperidin-H groups had lower lung histopathological scores,lower W/D and mononuclear macrophages,lymphocytes,neutrophils and the number of white blood cells in alveolar lavage fluid were decreased gradually,and expression levels of inflammatory mediators TNF-α,IL-1β,IL-6 and iNOS mRNA in lung tissue were gradually decreased,so as the contents of TNF-α,IL-1βand IL-6,level of apoptosis were gradually decreased,protein expression levels of Bax,c-caspase-3,p-STAT3/STAT3,p-JAK2/JAK2 and p-JAK1/JAK1 were gradually decreased,while expression level of Bcl-2 protein was gradually increased,the difference was statistically significant(P<0.05).Conclusion:Hesperidin can improve lung inflammation and reduce cell apoptosis in rats with severe pneumonia.