虫草芪参胶囊治疗百草枯染毒大鼠肺损伤的实验研究

发布时间：2018-05-30 20:02

本文选题：百草枯 + 虫草芪参胶囊　；参考：《山东大学》2014年硕士论文

【摘要】：背景：百草枯,又名“克无踪”、“对草快”,化学名为1,1-二甲基-4,4-联吡啶阳离子盐,为有机杂环类非选择性接触性除草剂,与土壤接触后可以迅速灭活,无大气污染和残留,价格便宜,除草效果好,在广大农业国家被广泛应用。由于接触的机会较多,每年自杀服用或误服接触的人数居高不下。百草枯摄入后,肺、肝、肾、心脏、甲状腺、肌肉组织甚至中枢神经系统都会受到损害,能导致全身多脏器功能不全,其主要靶器官是肺,能导致急性肺损伤,晚期形成肺间质纤维化。临床表现为接触部位糜烂或溃疡、进行性呼吸困难、肾功能损伤、肝功能损伤等。早期严重的肺渗出、水肿及晚期肺纤维化造成的呼吸衰竭是百草枯中毒后导致死亡的最主要原因。百草枯诱发肺损伤的机制目前尚不明确。百草枯中毒无特效解毒剂,因此,百草枯中毒的基础和临床研究具有重要的意义。虫草芪参是一种胶囊剂,内容物为灰褐色的粉末,气微腥,味微苦。其成分包括冬虫夏草、黄芪、丹参、红花、酸枣仁(炒)。药理研究证实,对于家兔Ma Sugi肾炎模型和大鼠异种血清免疫复合物型肾炎动物模型,可降低尿中白蛋白,升高血清白蛋白,减轻肾脏免疫复合物沉积,可以补肺益肾,活血化瘀,中医用于肺肾气虚、淤血阻滞。西医多应用于肺纤维化、肺动脉高压、免疫相关肾损伤的治疗,能减轻急性损伤时各种炎症因子的释放,改善肺部血流动力学,增加运动耐量,提高患者的生活质量。目前尚没有虫草芪参胶囊治疗百草枯中毒肺损伤的相关实验研究的报道。目的：建立大鼠百草枯染毒肺损伤模型,研究虫草芪参胶囊在百草枯诱导的肺损伤中的治疗作用。方法：成年雄性Wister大鼠90只,随机分为三组：百草枯染毒组,实验开始一次性给予20%百草枯原液灌胃50mg/kg大鼠体重；百草枯+虫草芪参胶囊治疗组,实验开始一次性给予20%百草枯原液灌胃50mg/kg大鼠体重,然后每天给予虫草芪参胶囊混悬液2ml/kg(目当于虫草芪参胶囊粉剂90mg/kg)大鼠体重；空白对照组给予等量生理盐水灌胃。实验结束分别于第7、14、21、28天麻醉后处死大鼠,动物呼吸停止之前取静脉血、肺泡灌洗液,检测血清及肺泡灌洗液还原性谷胱甘肽(GSH)、超氧化物歧化酶(SOD)水平,酶联免疫吸附法(ELISA)检测肺泡灌洗液肿瘤坏死因子(TNF-α)水平。留取大鼠肺组织,检测转化生长因子(TGF-β1)和羟脯氨酸(HYP)。留取部分肺组织做病理切片,并做HE和MASSON染色,光学显微镜下对比观察。结果：染毒组实验动物血清、肺泡灌洗液的GSH、SOD较空白对照降低,肺部组织TNF-α、TGF-β1、羟脯氨酸较空白对照组升高,差异有统计学意义。14天、21天、28天虫草芪参胶囊治疗组较相同天数染毒组GSH、SOD升高,TNF-α、TGF-β1及羟脯氨酸降低,差异有统计学意义。光学显微镜观察,染毒组肺组织损伤随着实验天数增加而加重,炎症细胞浸润程度逐渐增加,肺泡间隔纤维化在观察后期逐渐形成。治疗组较相同天数染毒组实验动物肺组织炎症程度、纤维化程度轻。结论：虫草芪参胶囊有明显的抗氧化作用,能减少细胞炎性因子的释放,减轻肺间质的损伤,治疗百草枯中毒引起的急性肺损伤和肺纤维化有一定疗效。
[Abstract]:Background: Paraquat, also known as "no trace", "to grass fast", the chemical name is 1,1- two methyl -4,4- bipyridine cationic salt, as an organic heterocyclic non selective contact herbicide, after contact with soil can be quickly inactivated, no atmospheric pollution and residue, cheap, good weeding effect, widely used in the vast agricultural countries. Due to contact The number of chances is more, the number of people who take or misuse the contact every year is high. After the intake of paraquat, the lung, liver, kidney, heart, thyroid, muscle tissue and even the central nervous system can be damaged, which can cause multiple organ dysfunction, the main target organ is lung, can cause acute lung injury, and later form pulmonary fibrosis in the late stage. The main causes of death caused by paraquat poisoning are early severe pulmonary exudation, edema and advanced pulmonary fibrosis. The mechanism of lung injury induced by paraquat is not yet clear. Paraquat poisoning has no specific solution. As a result, the basic and clinical research of paraquat poisoning is of great significance. Cordyceps Astragalus is a capsule with a brown powder, microfishy and bitter taste. Its components include Cordyceps sinensis, Astragalus membranaceus, Salvia miltiorrhiza, saffron and Zizyphus Zizyphi (stir fry). The pharmacological studies have proved that the Ma Sugi nephritis model of rabbits and the immunization of different serum in rats The animal model of compound glomerulonephritis can reduce albumin in urine, increase serum albumin, reduce the deposition of renal immune complex, make up the lungs and kidney, promote blood circulation and remove stasis, and use it in lung kidney qi deficiency and congestion. Western medicine is used in the treatment of pulmonary fibrosis, pulmonary hypertension and immune related renal injury, which can reduce the various inflammatory causes in acute injury. The release of the child can improve the pulmonary hemodynamics, increase the exercise tolerance and improve the quality of life of the patients. There is no report on the related experimental study on the treatment of paraquat induced lung injury by Cordyceps Astragalus capsule.
Objective: to establish a rat model of paraquat induced lung injury and study the therapeutic effect of Cordyceps sinensis Capsule on paraquat induced lung injury.
Methods: 90 adult male Wister rats were randomly divided into three groups: paraquat exposure group. The experiment began to give the weight of 50mg/kg rats with 20% paraquat original solution, and paraquat + Cordyceps Astragalus capsule treatment group. The experiment began to give 20% paraquat original solution to the weight of 50mg/kg rats, and then give the Cordyceps astragalus capsule every day. The body weight of the suspensions 2ml/kg (in the eyes of Astragalus Astragalus capsule powder 90mg/kg) was given in rats; the blank control group was given the same amount of normal saline for gavage. The end of the experiment was executed in rats after 7,14,21,28 Gastrodia drunken, and the blood was taken before the respiratory arrest and the alveolar lavage fluid was used to detect the reduced glutathione (GSH) and superoxide in the serum and the alveolar lavage fluid. The level of dismutase (SOD) and enzyme linked immunosorbent assay (ELISA) was used to detect the level of tumor necrosis factor (TNF- alpha) in alveolar lavage. The lung tissue of rats was retained and the transforming growth factor (TGF- beta 1) and hydroxyproline (HYP) were detected. Some lung tissues were taken for pathological section and were stained with HE and MASSON, and the contrast was observed under the optical microscope.
Results: the GSH and SOD of the alveolar lavage liquid were lower than that of the blank control. The lung tissue was TNF- alpha, TGF- beta 1, and the hydroxyproline was higher than that in the blank control group. The difference was statistically significant.14 days, 21 days, and the 28 days of the 28 days of the treatment group was higher than the same day group GSH, SOD increased, TNF- a, TGF- beta 1 and hydroxyproline decreased. The damage of lung tissue in the infected group was increased with the increase of the number of experimental days, the degree of infiltration of inflammatory cells gradually increased, and the alveolar septum fibrosis was gradually formed in the later period of observation.
Conclusion: Cordyceps Astragalus capsule has obvious antioxidation effect. It can reduce the release of inflammatory cytokines, reduce the injury of pulmonary interstitial, and treat acute lung injury and pulmonary fibrosis caused by paraquat poisoning.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R285.5

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