本文選題：抗結(jié)核藥物 + 肝損害�。� 參考：《河北北方學(xué)院》2013年碩士論文

【摘要】：基因多態(tài)性是藥物性肝損害的一個重要的風(fēng)險因素之一,抗結(jié)核藥導(dǎo)致肝損害與基因多態(tài)性的研究是目前臨床藥理學(xué)研究的熱點之一該項課題是對GSTM1和GSTT1無效基因型與結(jié)核病患者服用抗結(jié)核藥導(dǎo)致肝損害的關(guān)系的研究,探討這兩個基因的無效基因型是否是導(dǎo)致肝損害的高風(fēng)險因素。 收集解放軍第309醫(yī)院全軍結(jié)核病研究所臨床科室中服用異煙肼(INH)、利福平(RFP)、吡嗪酰胺(PZA)抗結(jié)核藥的結(jié)核病患者血標(biāo)本180例。根據(jù)年齡、性別、既往病史等條件進行綜合打分,排除不符合的病例。最后篩選出124例患者納入實驗室實驗階段,其中肝損害患者(E組99例)。分成三組,分別包括：輕度肝損害者(B組46例)、中度肝損害者(C組23例)、重度肝損害者(D組30例)。對照組：非肝損害者(A組25例)。性別組成：男性64例、女性60例,年齡范圍14-72歲。采血為外周血,放入EDTA管中,放置-4℃冰箱中，12h-36h內(nèi)完成DNA提取,采用聚合酶鏈反應(yīng)(PCR)進行DNA擴增。PCR的條件：GSTM1:94℃預(yù)變性5min；94℃變性60s,60℃退火60s,72℃延伸90s,循環(huán)35次；最后72℃延伸7min。GSTT1:94℃預(yù)變性4min；94℃變性45s,60℃退火45s,72℃延伸45s,循環(huán)35次；最后72℃延伸7min。分析GSTM1及GSTT1無效基因型分布頻率 通過T-test分析：B、C、D、E組的GSTM1基因分布頻率存在顯著性差異(P0.01); B、D、E組.的GSTT1的基因分布頻率存在顯著性差異(P0.01)；C組GSTT1基因分布頻率無顯著性差異(P0.05),本實驗經(jīng)偏札相關(guān)分析：GSTM1(r=0.204,P0.01)、GSTT1(r=0.204,P0.01)無效基因型分布頻率與非肝損害之間無顯著相關(guān)性；GSTM1(r=0.588, P0.01)、GSTT1(r=0.558, P0.01)無效基因分布頻率與輕度肝損害之間有顯著相關(guān)性；GSTM1(r=0.693, P0.01)、GSTT1(r=0.625,P0.01)無效基因分布頻率與中度肝損害之間有顯著相關(guān)性；GSTM1(r=0.590, P0.01)、GSTT1(r=0.550,P0.01),無效基因分布頻率與重度肝損害之間有顯著相關(guān)性；GSTM1(r=0.835, P0.01)、GSTT1(r=0.845, P0.01)無效基因分布頻率與肝損害(輕、中、重)之間有顯著相關(guān)性。 GSTM1、GSTT1無效基因型分別與服用抗結(jié)核藥導(dǎo)致肝損害有明顯統(tǒng)計學(xué)差異,即：GSTM1、GSTT1基因多態(tài)性與抗結(jié)核藥導(dǎo)致肝損害呈正相關(guān)。
[Abstract]:Gene polymorphism is one of the important risk factors for drug-induced liver damage. The study of liver damage and gene polymorphism induced by antituberculotics is one of the hot topics in clinical pharmacology. The study is concerned with the relationship between the invalid genotypes of GSTM1 and GSTT1 and liver damage induced by anti-tuberculosis drugs in patients with tuberculosis. To investigate whether the invalid genotypes of these two genes are high risk factors for liver damage. The blood samples of 180 tuberculosis patients taking isoniazid (INH), rifampicin (RFP) and pyrazinamide (PZA) were collected. According to the age, gender, past medical history and other conditions for comprehensive scoring, excluding the case. 124 patients were selected to be included in the laboratory experiment, including 99 patients with liver injury (group E). They were divided into three groups: mild liver injury (group B, 46 cases), moderate liver injury (group C, 23 cases) and severe liver damage (group D, 30 cases). Control group: non-hepatic injury (group A, 25 cases). Sex composition: 64 males and 60 females aged 14-72 years. Blood was collected from peripheral blood and placed in EDTA tube. DNA extraction was completed within 12h-36 h in refrigerator at -4 鈩，

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