Tang Lu-ping, Xiao Wei, Li Yi-fang, Li Hai-bo, Wang Zhen-zhong, Yao Xin-sheng, Kurihara Hiroshi, He Rong-rong
Pharmacy College, Jinan University, Guangzhou, 510632, China.
Chin J Integr Med. 2014 Aug;20(8):591-9. doi: 10.1007/s11655-014-1758-x. Epub 2014 Jun 10.
To evaluate the protective effects of Reduning Injection (, RDN), a patent Chinese medicine, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and its underlying mechanisms of action.
Sixty male Sprague-Dawley rats were randomly divided into 6 groups, including normal control, model, dexamethasone (DEX, 5 mg/kg), RDN-H (720 mg/kg), RDN-M (360 mg/kg) and RDN-L (180 mg/kg) groups, with 10 rats in each group. Rats were challenged with intravenous injection of LPS 1 h after intraperitoneal treatment with RDN or DEX. At 6 h after LPS challenge, lung tissues and bronchoalveolar lavage fluid (BALF) were collected, and the number of inflammatory cells was determined. The right lungs were collected for histopathologic examination, measurement of gene and protein expressions, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities.
In vivo pretreatment of RDN (360, 720 mg/kg) significantly reduced the weight of wet to dry (W/D) ratio of lung, protein content in BALF, and led to remarkable attenuation of LPS-induced histopathological changes in the lungs. Meanwhile, RDN enormously decreased BALF total inflammatory cells, especially neutrophil and macrophage cell numbers. Moreover, RDN increased SOD activity, inhibited MPO activity, alleviated LPS-induced tumor neurosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression in lung tissues. Furthermore, RDN (720 mg/kg) efficiently weakened nuclear factorkappa B (NF-κB) gene and protein expression.
Anti-inflammatory effects of RDN was demonstrated to be preventing pulmonary neutrophil infiltration, lowering MPO activity, TNF-α and iNOS gene expression by inhibiting NF-κB activity in LPS-induced ALI.
评价专利中药热毒宁注射液(RDN)对脂多糖(LPS)诱导的大鼠急性肺损伤(ALI)的保护作用及其潜在作用机制。
将60只雄性Sprague-Dawley大鼠随机分为6组,包括正常对照组、模型组、地塞米松(DEX,5mg/kg)组、热毒宁高剂量(RDN-H,720mg/kg)组、热毒宁中剂量(RDN-M,360mg/kg)组和热毒宁低剂量(RDN-L,180mg/kg)组,每组10只。在腹腔注射RDN或DEX 1小时后,通过静脉注射LPS对大鼠进行攻击。在LPS攻击后6小时,收集肺组织和支气管肺泡灌洗液(BALF),并测定炎症细胞数量。收集右肺进行组织病理学检查、基因和蛋白表达测定、超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)活性测定。
体内预先给予RDN(360、720mg/kg)可显著降低肺组织湿/干(W/D)比值、BALF中蛋白含量,并显著减轻LPS诱导的肺组织病理学变化。同时,RDN可显著减少BALF中总炎症细胞数量,尤其是中性粒细胞和巨噬细胞数量。此外,RDN可提高SOD活性,抑制MPO活性,减轻LPS诱导的肺组织中肿瘤坏死因子-α(TNF-α)和诱导型一氧化氮合酶(iNOS)表达。此外,RDN(720mg/kg)可有效减弱核因子κB(NF-κB)基因和蛋白表达。
在LPS诱导的ALI中,热毒宁的抗炎作用表现为通过抑制NF-κB活性来防止肺中性粒细胞浸润,降低MPO活性、TNF-α和iNOS基因表达。