沈赵赟 符胜光 杨爱东 吴中华 李素云 帅玉叶 唐普仁

摘要：目的 觀察加味千金苇茎汤对大气细颗粒物致肺组织损伤大鼠肿瘤坏死因子-α（TNF-α）和核因子-κB（NF-κB）的影响，探讨其可能的作用机制。方法 大鼠气管滴注15 mg/kg细颗粒物生理盐水混悬液造模，隔日1次，共3次。将32只Wistar大鼠随机分为正常组、模型组和加味千金苇茎汤高、低剂量组，每组8只，给药组每日给予相应剂量药物灌胃。ELISA检测支气管肺泡灌洗液TNF-α水平，免疫组化检测肺组织NF-κB蛋白表达，光镜下观察大鼠肺组织病理变化。结果 与正常组比较，模型组大鼠肺泡灌洗液TNF-α含量及肺组织NF-κB蛋白表达显著升高（P<0.01）；与模型组比较，加味千金苇茎汤低、高剂量组大鼠肺泡灌洗液TNF-α含量及肺组织NF-κB蛋白表达显著降低（P<0.05，P<0.01）。病理观察结果显示，模型组较正常组小气管内、肺泡及肺间质内有大量细颗粒物沉着，肺泡及肺间质内可见大量吞噬细颗粒物的巨噬细胞并伴有较多中性粒细胞和淋巴细胞浸润；加味千金苇茎汤高、低剂量组肺组织病理改变明显轻于模型组，高剂量组炎症反应较轻，肺泡及肺间质内可见吞噬细颗粒物的巨噬细胞、少量中性粒细胞和淋巴细胞浸润。结论 加味千金苇茎汤可能通过降低TNF-α含量、下调NF-κB蛋白表达，以减轻模型大鼠的肺组织损伤，对肺组织有保护作用。

关键词：加味千金苇茎汤；细颗粒物；肺损伤；肿瘤坏死因子-α；核因子-κB；大鼠

DOI：10.3969/j.issn.1005-5304.2018.01.009

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2018）01-0038-05

Effects of Modified Qianjin Weijing Decoction on TNF-α and NF-κB

in Rats with Lung Injury Induced by Particulate Matter

SHEN Zhao-yun， FU Sheng-guang， YANG Ai-dong， WU Zhong-hua， LI Su-yun， SHUAI Yu-ye， TANG Pu-ren Shanghai University of Traditional Chinese Medicine， Shanghai 201203， China

Abstract： Objective To investigate the protective effect of modified Qianjin Weijing Decoction （MQJWJD） on TNF-α and NF-κB in rats with lung injury induced by particulate matter； To discuss relevant mechanism of action. Methods A tracheal drip 15 mg/kg fine particles of saline solution was used to establish modeling， every other day， three times. Thirty-two Wistar rats were randomly divided into normal group， model group and MQJWJD high-dose and low-dose groups， with eight rats in each group. Medication groups were given relevant medicine for gavage. The level of TNF-α in bronchoalveolar lavage fluid （BALF） was measured by ELISA. The expression of NF-κB protein in lung tissues was measured by immunohistochemistry. The histopathology of the lung injury was observed by light microscope. Results Compared with normal group， the level of TNF-α and the expression of NF-κB protein in the model group were higher than those in the normal group （P<0.01）. Compared with model group， the level of TNF-α and the expression of NF-κB protein in MQJWJD low-dose and high-dose groups were lower than those in the model group （P<0.05， P<0.01）. Pathological observation showed that， compared with normal group， model group showed intratracheal， alveolar and interstitial bacteria within a large number of fine particles calm， alveolar and pulmonary interstitial visible large amounts of phagocytic fine particles of macrophages and accompanied by more neutrophils

基金项目：国家自然科学金面上项目（81673855）；国家中医药管理局重点学科项目（2009年）；上海市重点学科建设资助项目（S30301）；上海中医药大学第9批大学生科创资助项目（SHUTCM2016177）；上海中医药大学名师研究室项目（A1-Z173020711）；上海中医药大学基础医学院与曙光医院院院合作项目（2015年）；上海中医药大学德育渗透课题（A1-60102009）

通讯作者：杨爱东，E-mail：aidongy@126.com

and lymphocyte infiltration； Lung tissue pathological changes were significantly lighter in MQJWJD high-dose and low-dose groups than the model group. MQJWJD high-dose group showed mild inflammation， alveolar and pulmonary interstitial visible phagocytic fine particles of macrophages， a small amount of neutrophils and lymphocyte infiltration. Conclusion MQJWJD can reduce the pulmonary injury in rats induced by particulate matter and has protective effects on the rat model through decreasing the levels of TNF-α and the expressions of NF-κB protein in injured lung tissues.

Keywords： modified Qianjin Weijing Decoction； particulate matter； pulmonary injury； TNF-α； NF-κB； rats

研究表明，大氣细颗粒物暴露与肺癌具有明显的相关性，大气中细颗粒物浓度每增加10 μg/m3，肺癌死亡率可增加15%～27%[1]。有文献报道，颗粒物致肺损伤的机制之一是导致机体发生炎性损伤[2]。肿瘤坏死因子-α（TNF-α）是炎症反应中重要的启动因子，核因子-κB（NF-κB）是免疫调控信号通路中重要的转录调控因子，二者在炎性反应过程中起着重要作用。……