中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2015年
22期
1726-1730
,共5页
王胜%熊玲玲%邓雪%任薇%朱春冬%李春颖%周群
王勝%熊玲玲%鄧雪%任薇%硃春鼕%李春穎%週群
왕성%웅령령%산설%임미%주춘동%리춘영%주군
肺疾病,慢性阻塞性%辛伐他汀%气道炎症%气道黏液高分泌%大鼠
肺疾病,慢性阻塞性%辛伐他汀%氣道炎癥%氣道黏液高分泌%大鼠
폐질병,만성조새성%신벌타정%기도염증%기도점액고분비%대서
Pulmonary disease,chronic obstructive%Simvastatin%Airway inflammation%Airway mucus hypersecretion%Rats
目的 探讨辛伐他汀对慢性阻塞性肺疾病(慢阻肺)模型大鼠气道炎症和气道黏液高分泌的防治作用及其机制.方法 采用烟熏和大鼠气管内注入脂多糖的方法建立慢阻肺模型.将18只雄性SD大鼠按随机数字表法随机均分为对照组、慢阻肺组、辛伐他汀组各6只.对照组和慢阻肺组用生理盐水1 ml/100 g灌胃,1次/d;辛伐他汀组用辛伐他汀溶液(0.5 g/L)1 ml/100 g灌胃,1次/d.肺功能仪检测大鼠肺功能,HE染色观察大鼠支气管、肺组织病理变化.酶联免疫吸附(ELISA)法检测各组大鼠支气管肺泡灌洗液(BALF)中白细胞介素(IL)-8、IL-17及肿瘤坏死因子(TNF)-α含量.免疫组织化学法检测大鼠气道中黏附分子1、核因子(NF)-κB、黏蛋白5AC和Toll样受体4(TLR4)蛋白的表达.Western印迹法检测大鼠支气管肺组织中黏蛋白5AC和TLR4蛋白的表达.荧光实时定量(RT)-PCR检测大鼠支气管肺组织中黏蛋白5AC mRNA和TLR4 mRNA的表达.结果 慢阻肺组支气管、肺组织改变符合慢阻肺的病理表现.与对照组相比,辛伐他汀组支气管肺组织均出现不同程度损伤,但损伤程度轻于慢阻肺组.辛伐他汀组肺功能显著低于对照组,但优于慢阻肺组.辛伐他汀组BALF中IL-8、IL-17、TNF-α含量分别为(484.4±11.1)、(78.9±2.0)、(192.7±2.0)ng/L,均显著低于慢阻肺组的(605.0 ±48.7)、(89.9±6.9)、(212.6±10.7)ng/L,但均显著高于对照组的(341.2±21.4)、(56.0±2.9)、(127.5±9.0)ng/L(均P＜0.01).辛伐他汀组支气管肺组织中黏附分子1、NF-κB、黏蛋白5AC和TLR4蛋白的表达均显著低于慢阻肺组,但均显著高于对照组(均P＜0.01).辛伐他汀组支气管肺组织中黏蛋白5AC mRNA和TLR4 mRNA及其蛋白的表达均显著低于慢阻肺组(均P＜0.05).结论 辛伐他汀可降低慢阻肺模型大鼠BALF中IL-8、IL-17、TNF-α水平,抑制气道和肺组织内黏附分子1、NF-κB、黏蛋白5AC和TLR4蛋白的表达,减轻气道炎症和气道黏液高分泌.
目的 探討辛伐他汀對慢性阻塞性肺疾病(慢阻肺)模型大鼠氣道炎癥和氣道黏液高分泌的防治作用及其機製.方法 採用煙熏和大鼠氣管內註入脂多糖的方法建立慢阻肺模型.將18隻雄性SD大鼠按隨機數字錶法隨機均分為對照組、慢阻肺組、辛伐他汀組各6隻.對照組和慢阻肺組用生理鹽水1 ml/100 g灌胃,1次/d;辛伐他汀組用辛伐他汀溶液(0.5 g/L)1 ml/100 g灌胃,1次/d.肺功能儀檢測大鼠肺功能,HE染色觀察大鼠支氣管、肺組織病理變化.酶聯免疫吸附(ELISA)法檢測各組大鼠支氣管肺泡灌洗液(BALF)中白細胞介素(IL)-8、IL-17及腫瘤壞死因子(TNF)-α含量.免疫組織化學法檢測大鼠氣道中黏附分子1、覈因子(NF)-κB、黏蛋白5AC和Toll樣受體4(TLR4)蛋白的錶達.Western印跡法檢測大鼠支氣管肺組織中黏蛋白5AC和TLR4蛋白的錶達.熒光實時定量(RT)-PCR檢測大鼠支氣管肺組織中黏蛋白5AC mRNA和TLR4 mRNA的錶達.結果 慢阻肺組支氣管、肺組織改變符閤慢阻肺的病理錶現.與對照組相比,辛伐他汀組支氣管肺組織均齣現不同程度損傷,但損傷程度輕于慢阻肺組.辛伐他汀組肺功能顯著低于對照組,但優于慢阻肺組.辛伐他汀組BALF中IL-8、IL-17、TNF-α含量分彆為(484.4±11.1)、(78.9±2.0)、(192.7±2.0)ng/L,均顯著低于慢阻肺組的(605.0 ±48.7)、(89.9±6.9)、(212.6±10.7)ng/L,但均顯著高于對照組的(341.2±21.4)、(56.0±2.9)、(127.5±9.0)ng/L(均P＜0.01).辛伐他汀組支氣管肺組織中黏附分子1、NF-κB、黏蛋白5AC和TLR4蛋白的錶達均顯著低于慢阻肺組,但均顯著高于對照組(均P＜0.01).辛伐他汀組支氣管肺組織中黏蛋白5AC mRNA和TLR4 mRNA及其蛋白的錶達均顯著低于慢阻肺組(均P＜0.05).結論 辛伐他汀可降低慢阻肺模型大鼠BALF中IL-8、IL-17、TNF-α水平,抑製氣道和肺組織內黏附分子1、NF-κB、黏蛋白5AC和TLR4蛋白的錶達,減輕氣道炎癥和氣道黏液高分泌.
목적 탐토신벌타정대만성조새성폐질병(만조폐)모형대서기도염증화기도점액고분비적방치작용급기궤제.방법 채용연훈화대서기관내주입지다당적방법건립만조폐모형.장18지웅성SD대서안수궤수자표법수궤균분위대조조、만조폐조、신벌타정조각6지.대조조화만조폐조용생리염수1 ml/100 g관위,1차/d;신벌타정조용신벌타정용액(0.5 g/L)1 ml/100 g관위,1차/d.폐공능의검측대서폐공능,HE염색관찰대서지기관、폐조직병리변화.매련면역흡부(ELISA)법검측각조대서지기관폐포관세액(BALF)중백세포개소(IL)-8、IL-17급종류배사인자(TNF)-α함량.면역조직화학법검측대서기도중점부분자1、핵인자(NF)-κB、점단백5AC화Toll양수체4(TLR4)단백적표체.Western인적법검측대서지기관폐조직중점단백5AC화TLR4단백적표체.형광실시정량(RT)-PCR검측대서지기관폐조직중점단백5AC mRNA화TLR4 mRNA적표체.결과 만조폐조지기관、폐조직개변부합만조폐적병리표현.여대조조상비,신벌타정조지기관폐조직균출현불동정도손상,단손상정도경우만조폐조.신벌타정조폐공능현저저우대조조,단우우만조폐조.신벌타정조BALF중IL-8、IL-17、TNF-α함량분별위(484.4±11.1)、(78.9±2.0)、(192.7±2.0)ng/L,균현저저우만조폐조적(605.0 ±48.7)、(89.9±6.9)、(212.6±10.7)ng/L,단균현저고우대조조적(341.2±21.4)、(56.0±2.9)、(127.5±9.0)ng/L(균P＜0.01).신벌타정조지기관폐조직중점부분자1、NF-κB、점단백5AC화TLR4단백적표체균현저저우만조폐조,단균현저고우대조조(균P＜0.01).신벌타정조지기관폐조직중점단백5AC mRNA화TLR4 mRNA급기단백적표체균현저저우만조폐조(균P＜0.05).결론 신벌타정가강저만조폐모형대서BALF중IL-8、IL-17、TNF-α수평,억제기도화폐조직내점부분자1、NF-κB、점단백5AC화TLR4단백적표체,감경기도염증화기도점액고분비.
Objective To explore the preventive and therapeutic effects of simvastatin on rats with chronic obstructive pulmonary disease (COPD) and examine the mechanism of airway inflammation and airway mucus hypersecretion.Methods The rat model of COPD was established by cigarette smoking and an intratracheal injection of lipopolysaccharide (LPS).A total of 18 male Sprague-Dawley rats were randomly divided into control,COPD and simvastatin groups (n =6 each).The control and COPD groups received normal saline once daily via intragastric administration (i.g.) while the simvastatin group had simvastatin (0.5 g/L) 1 ml/100 g once daily via i.g.Pulmonary function was tested and pathological changes in bronchus and lung were observed.The bronchoalveolar lavage fluid (BALF) levels of interleukin-8 (IL-8),interleukin-17 (IL-17) and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA).The protein expressions of intercellular adhesion molecule 1 (ICAM-1),nuclear factor κB (NF-κB),mucin 5AC (MUC5AC) and Toll-like receptor 4 (TLR4) in rat airway were detected by immunohistochemical staining.The mRNA and protein expressions of TLR4 and MUC5AC in bronchi and lung tissue were detected by fluorescent real time quantitative polymerase chain reaction (RT-PCR) and Western blot.Results The changes of bronchi and lung tissues in COPD group were consistent with typical pathological manifestations of COPD.As compared with the COPD group,the degree of pulmonary pathological damage and the decline of pulmonary function in the simvastatin group were significantly lessened,but still remarkable as compared with the control group.The BALF levels of IL-8,IL-17 and TNF-α in the smvastatin group [(484.4 ± 11.1),(78.9 ± 2.0),(192.7 ± 2.0) ng/L] were significantly lower than those in the COPD group [(605 ±48.7),(89.9 ±6.9),(212.6 ± 10.7) ng/L],but still higher than those in the control group [(341.2 ± 21.4),(56.0 ± 2.9),(127.5 ± 9.0) ng/L respectively] (all P＜0.01).Compared with COPD group,the expression levels of ICAM-1,NF-κB,MUC5AC and TLR4 protein were significantly lower in the simvastatin group,but still higher than the control group (all P ＜0.01).Furthermore,the expression levels of mRNA and protein of MUC5AC and TLR4 were significantly lower in the simvastatin group than those in the COPD group (all P ＜ 0.05).Conclusions In COPD model rats,simvastatin can decrease the levels of IL-8,IL-17 and TNF-α in BALF and inhibit the expression levels of ICAM-1,NF-κB,MUC5AC and TLR4 protein in airway and lung tissue.Thus it plays preventive and therapeutic roles by reducing airway inflammation and airway mucus hypersecretion.
