蟲(chóng)草芪參膠囊治療百草枯染毒大鼠肺損傷的實(shí)驗(yàn)研究
本文選題:百草枯 + 蟲(chóng)草芪參膠囊; 參考:《山東大學(xué)》2014年碩士論文
【摘要】:背景:百草枯,又名“克無(wú)蹤”、“對(duì)草快”,化學(xué)名為1,1-二甲基-4,4-聯(lián)吡啶陽(yáng)離子鹽,為有機(jī)雜環(huán)類(lèi)非選擇性接觸性除草劑,與土壤接觸后可以迅速滅活,無(wú)大氣污染和殘留,價(jià)格便宜,除草效果好,在廣大農(nóng)業(yè)國(guó)家被廣泛應(yīng)用。由于接觸的機(jī)會(huì)較多,每年自殺服用或誤服接觸的人數(shù)居高不下。百草枯攝入后,肺、肝、腎、心臟、甲狀腺、肌肉組織甚至中樞神經(jīng)系統(tǒng)都會(huì)受到損害,能導(dǎo)致全身多臟器功能不全,其主要靶器官是肺,能導(dǎo)致急性肺損傷,晚期形成肺間質(zhì)纖維化。臨床表現(xiàn)為接觸部位糜爛或潰瘍、進(jìn)行性呼吸困難、腎功能損傷、肝功能損傷等。早期嚴(yán)重的肺滲出、水腫及晚期肺纖維化造成的呼吸衰竭是百草枯中毒后導(dǎo)致死亡的最主要原因。百草枯誘發(fā)肺損傷的機(jī)制目前尚不明確。百草枯中毒無(wú)特效解毒劑,因此,百草枯中毒的基礎(chǔ)和臨床研究具有重要的意義。蟲(chóng)草芪參是一種膠囊劑,內(nèi)容物為灰褐色的粉末,氣微腥,味微苦。其成分包括冬蟲(chóng)夏草、黃芪、丹參、紅花、酸棗仁(炒)。藥理研究證實(shí),對(duì)于家兔Ma Sugi腎炎模型和大鼠異種血清免疫復(fù)合物型腎炎動(dòng)物模型,可降低尿中白蛋白,升高血清白蛋白,減輕腎臟免疫復(fù)合物沉積,可以補(bǔ)肺益腎,活血化瘀,中醫(yī)用于肺腎氣虛、淤血阻滯。西醫(yī)多應(yīng)用于肺纖維化、肺動(dòng)脈高壓、免疫相關(guān)腎損傷的治療,能減輕急性損傷時(shí)各種炎癥因子的釋放,改善肺部血流動(dòng)力學(xué),增加運(yùn)動(dòng)耐量,提高患者的生活質(zhì)量。目前尚沒(méi)有蟲(chóng)草芪參膠囊治療百草枯中毒肺損傷的相關(guān)實(shí)驗(yàn)研究的報(bào)道。 目的:建立大鼠百草枯染毒肺損傷模型,研究蟲(chóng)草芪參膠囊在百草枯誘導(dǎo)的肺損傷中的治療作用。 方法:成年雄性Wister大鼠90只,隨機(jī)分為三組:百草枯染毒組,實(shí)驗(yàn)開(kāi)始一次性給予20%百草枯原液灌胃50mg/kg大鼠體重;百草枯+蟲(chóng)草芪參膠囊治療組,實(shí)驗(yàn)開(kāi)始一次性給予20%百草枯原液灌胃50mg/kg大鼠體重,然后每天給予蟲(chóng)草芪參膠囊混懸液2ml/kg(目當(dāng)于蟲(chóng)草芪參膠囊粉劑90mg/kg)大鼠體重;空白對(duì)照組給予等量生理鹽水灌胃。實(shí)驗(yàn)結(jié)束分別于第7、14、21、28天麻醉后處死大鼠,動(dòng)物呼吸停止之前取靜脈血、肺泡灌洗液,檢測(cè)血清及肺泡灌洗液還原性谷胱甘肽(GSH)、超氧化物歧化酶(SOD)水平,酶聯(lián)免疫吸附法(ELISA)檢測(cè)肺泡灌洗液腫瘤壞死因子(TNF-α)水平。留取大鼠肺組織,檢測(cè)轉(zhuǎn)化生長(zhǎng)因子(TGF-β1)和羥脯氨酸(HYP)。留取部分肺組織做病理切片,并做HE和MASSON染色,光學(xué)顯微鏡下對(duì)比觀察。 結(jié)果:染毒組實(shí)驗(yàn)動(dòng)物血清、肺泡灌洗液的GSH、SOD較空白對(duì)照降低,肺部組織TNF-α、TGF-β1、羥脯氨酸較空白對(duì)照組升高,差異有統(tǒng)計(jì)學(xué)意義。14天、21天、28天蟲(chóng)草芪參膠囊治療組較相同天數(shù)染毒組GSH、SOD升高,TNF-α、TGF-β1及羥脯氨酸降低,差異有統(tǒng)計(jì)學(xué)意義。光學(xué)顯微鏡觀察,染毒組肺組織損傷隨著實(shí)驗(yàn)天數(shù)增加而加重,炎癥細(xì)胞浸潤(rùn)程度逐漸增加,肺泡間隔纖維化在觀察后期逐漸形成。治療組較相同天數(shù)染毒組實(shí)驗(yàn)動(dòng)物肺組織炎癥程度、纖維化程度輕。 結(jié)論:蟲(chóng)草芪參膠囊有明顯的抗氧化作用,能減少細(xì)胞炎性因子的釋放,減輕肺間質(zhì)的損傷,治療百草枯中毒引起的急性肺損傷和肺纖維化有一定療效。
[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.
【學(xué)位授予單位】:山東大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類(lèi)號(hào)】:R285.5
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