本文選題：異煙肼 + 利福平�。� 參考：《中南大學》2014年碩士論文

【摘要】：目的：研究異煙肼(INH)與利福平(RFP)單用及合用致小鼠肝損傷模型中對肝細胞上膽汁酸有關的轉運體Ntcp、Bsep表達的影響。探討利福平與異煙肼合用引起肝損傷加重是否與這些轉運體表達變化有關。方法：選用SPF級56只成年雌性ICR小鼠(ICR mouse)(29.8±1.4g),按照完全隨機分組原則分為7組,實驗組分別給與50mg/kg INH,100mg/kg RFP,50mg/kg+100mg/kg INH+RFP,100mg/kg INH,200mg/kg RFP,100mg/kg+200mg/kg INH+RFP,對照組給予空白溶劑,連續(xù)給藥2周,第15天將小鼠以水合氯醛麻醉,摘除眼球取血,離心取上清,用于肝功能生化指標測定,每組每只留取肝臟組織分別于10%福爾馬林固定用于病理切片、HE染色；4%多聚甲醛固定用于目標蛋白免疫組化測定；Western blot測定目標蛋白Ntcp及Bsep的表達。結果：高劑量INH+RFP能夠引起生化指標ALT、AST、TBil、DBil、ALP、TBA、MDA顯著變化,肝臟形態(tài)及病理結果顯示有肝損傷,低劑量INH、RFP、INH+RFP則變化較小。免疫組化及Western blot結果示對照組和各實驗組Ntcp及Bsep均有表達,單用組及合用組較正常對照組相比,Ntcp蛋白表達均下調(P0.01),H-INH+RFP較L-INH+RFP組Bsep表達明顯下調(P0.01)。Ntcp、Bsep蛋白的表達與血清中膽汁酸的分泌量呈負相關,相關系數(shù)分別為-0.320,-0.391,差異有統(tǒng)計學意義(P0.05)。結論：高劑量INH、RFP單用及合用均造成小鼠肝損傷,INH單用及與RFP合用均能有下調膽汁酸有關轉運體Ntcp及Bsep蛋白的表達,高劑量時對轉運體Bsep的表達影響更為明顯,INH單用及與RFP合用誘導小鼠肝損傷模型的血清生化指標與組織病理學的變化明顯滯后于轉運體的顯著變化,INH、RFP引起肝損傷病理狀態(tài)可能是轉運體與內源性物質(膽紅素、膽汁酸等)改變共同作用的結果。圖13幅,表4個,參考文獻89篇。
[Abstract]:Aim: to study the effect of isoniazid (INH) and rifampicin (RFP) alone or in combination on the expression of bile acid-related transporter NtcpnBsep in hepatocytes. To investigate whether rifampicin combined with isoniazid can aggravate liver injury and change the expression of these transporters. Methods: 56 adult female ICR mice of SPF grade were randomly divided into 7 groups according to the principle of complete randomized grouping. The experimental group was given 100 mg / kg 100mg/kg INH 100mg/kg INH 100 mg / kg 100mg/kg INH rpm 100 mg / kg 100mg/kg INH 100 mg / kg 200mg/kg INH RFP, respectively. The control group was given blank solvent for 2 weeks. On the 15th day, the mice were anesthetized with chloral hydrate, blood was removed from eyeball, supernatant was centrifuged, and used to determine the biochemical index of liver function. Each liver was fixed with 10% formalin for HE staining and 4% paraformaldehyde fixation to determine the expression of Ntcp and Bsep by immunohistochemistry. Results: high dose of INH RFP could cause significant changes of MDA in the biochemical index of ALTAST TBildlb TBAM, liver morphology and pathological results showed liver injury, while low dose of INHG RFPINH RFP showed little change. The results of immunohistochemistry and Western blot showed that Ntcp and Bsep were expressed in the control group and each experimental group. Compared with the control group, the expression of ntcp protein decreased significantly in the single group and the combination group compared with the control group. The expression of Bsep in the single group and the combination group was significantly lower than that in the group of L-INH RFP. There was a negative correlation between the expression of the protein and the secretion of bile acid in serum, the correlation coefficient was -0.320-0.391.The difference was significant (P 0.05). Conclusion: the expression of Ntcp and Bsep protein of bile acid-related transporter can be down-regulated by both high-dose INHP-RFP alone and its combination with RFP in mice liver injury. The effect of high dose on the expression of transporter Bsep was more obvious. The changes of serum biochemical indexes and histopathology in mice model of liver injury induced by INH alone and combined with RFP were obviously lagging behind the significant changes of transporter. The pathological state may be transporters and endogenous substances (bilirubin, bilirubin, Bile acids, etc.) change the result of a common action. 13 figures, 4 tables, 89 references.
【學位授予單位】：中南大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R965

【參考文獻】

相關期刊論文 前4條

1 陳成偉;;藥物性肝損害診斷標準的評價[J];診斷學理論與實踐;2009年02期

2 Meghna R Adhvaryu;Narsimha Reddy;Minoo H Parabia;;Effects of four Indian medicinal herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury and immunosuppression in guinea pigs[J];World Journal of Gastroenterology;2007年23期

3 María José Casanova-González;María Trapero-Marugán;E Anthony Jones;Ricardo Moreno-Otero;;Liver disease and erythropoietic protoporphyria:A concise review[J];World Journal of Gastroenterology;2010年36期

4 周利婷;周燕;張國強;魏玉輝;任江霞;武新安;;異煙肼對小鼠肝細胞膜轉運體Mrp2,Bsep,P-gp和Ntcp表達的影響[J];中國藥學雜志;2014年04期

，

本文編號：1879226