【摘要】：【目的】初步探索應(yīng)用肝毒性中藥黃藥子煎劑灌胃建立小鼠肝損傷模型，并從脂質(zhì)過氧化損傷方面分析其機制。 【方法】 （1）昆明種清潔級小鼠40只，體重18-22g，雌雄各半。隨機分為4組：空白組、黃藥子煎劑高劑量組、中劑量組、低劑量組，每組10只。黃藥子煎劑各組分別以240g·kg~(-1)、120g·kg~(-1)、60g·kg~(-1)，按0.2mL·10g~(-1)體重黃藥子煎劑灌胃；空白組以等體積蒸餾水灌胃。每日1次，連續(xù)灌胃6d后處死，分別檢測血清丙氨酸氨基轉(zhuǎn)移酶（alanine aminotransferase，ALT）、天門冬氨酸氨基轉(zhuǎn)移酶（aspertateaminotransferase，AST），計算肝指數(shù)，觀察肝組織普通病理形態(tài)學變化，以探索黃藥子煎劑致明顯肝損傷的相對合適劑量。 （2）昆明種清潔級小鼠30只，體重18-22g，雌雄各半。隨機分為3組：空白組、黃藥子煎劑給藥6d組、12d組，每組10只。黃藥子煎劑組以探索出的相對合適劑量黃藥子煎劑，按0.2mL·10g~(-1)體重灌胃；空白組給予等體積蒸餾水灌胃。每日1次，，給藥組連續(xù)灌胃6d、12d后分別處死10只，分別檢測血清ALT、AST、總膽紅素（total bilirubin，TBil），計算肝指數(shù)，觀察肝組織普通病理形態(tài)學變化，以確定致明顯肝損傷的相對合適時間。并檢測小鼠肝組織丙二醛（malondialdehyde，MDA）、谷胱甘肽過氧化物酶（glutathione peroxidase，GSH-Px），初步探討黃藥子致肝損傷的機理。 【結(jié)果】 （1）不同劑量黃藥子煎劑灌胃對小鼠血清ALT、AST、肝指數(shù)的影響：與空白組比較，各劑量組黃藥子煎劑對小鼠血清ALT、AST及肝指數(shù)均有明顯影響（P0.05）。高、中、低劑量三組之間兩兩比較，ALT的差異明顯，黃藥子劑量越大，ALT越高，與用藥劑量呈正相關(guān)（P0.05）；低與高、中劑量組間AST的差異有顯著意義（P0.05）；三組之間肝指數(shù)比較無顯著統(tǒng)計學意義（P0.05）。 （2）不同劑量黃藥子煎劑灌胃對小鼠肝組織形態(tài)學的影響：低劑量組小鼠未出現(xiàn)明顯肝損傷；中、高劑量組小鼠肝損傷明顯，尤以高劑量組為甚。經(jīng)肝細胞變性半定量分析，低劑量黃藥子煎劑灌胃對小鼠肝細胞無明顯影響（P0.005），高、中劑量組與空白組相比有顯著統(tǒng)計學意義（P0.005）。 （3）高劑量黃藥子煎劑灌胃不同時間對小鼠血清ALT、AST、TBil及肝指數(shù)的影響：6d、12d組小鼠血清ALT、AST、TBil及肝指數(shù)明顯升高，與空白組比較有顯著的統(tǒng)計學意義（P0.05）。但兩組之間無顯著統(tǒng)計學差異（P0.05）。 （4）高劑量黃藥子煎劑灌胃不同時間對肝組織形態(tài)學的影響：6d、12d組小鼠均出現(xiàn)明顯肝組織損傷。經(jīng)肝細胞變性半定量分析，高劑量黃藥子煎劑灌胃6d、12d與空白組比較均有顯著統(tǒng)計學意義（P0.005），但兩組之間比較無顯著統(tǒng)計學意義（P0.005）。 （5）高劑量黃藥子煎劑灌胃6d對小鼠肝組織MDA、GSH-Px的影響：與空白組比較，高劑量黃藥子煎劑灌胃6d對小鼠肝組織MDA和GSH-Px水平影響不大，無顯著統(tǒng)計學意義（P0.05）。 【結(jié)論】（1）應(yīng)用高劑量（240g·kg~(-1)）黃藥子煎劑灌胃6d可造成小鼠明顯肝損傷。（2）自由基脂質(zhì)過氧化可能沒有參與黃藥子煎劑誘導的肝損傷，但仍需在以后的實驗中進一步確定。
[Abstract]:[Objective] To establish a model of liver injury in mice by intragastric administration of Huangyaozi decoction, a hepatotoxic Chinese herb, and analyze its mechanism from the aspect of lipid peroxidation injury.
[method]
(1) 40 clean grade mice in Kunming, weighing 18-22g, and male and female, were divided into 4 groups randomly: blank group, high dose group of xanthate decoction, middle dose group, low dose group, 10 rats in each group. Each group of xanthate decoctions was treated with 240g kg~ (-1), 120g. Kg~ (-1), 60g. 1 times a day and 1 times a day after continuous perfusion of the stomach, the serum alanine aminotransferase (alanine aminotransferase, ALT), aspartate aminotransferase (aspertateaminotransferase, AST), the liver index were calculated and the normal pathological changes of liver tissue were observed in order to explore the relative appropriate liver damage caused by the decoction of xanthate. Dose.
(2) 30 clean grade mice in Kunming, weighing 18-22g, and male and female, were randomly divided into 3 groups: blank group, 6D group of xanthate decoction, group 12D, 10 in each group. The relative suitable dosage of xanthate decoction, 0.2mL. 10g~ (-1) weight was given to the stomach. The blank group was given equal volume distilled water for gastric perfusion. 1 times a day, the group was connected to the drug group. After continuous perfusion of 6D and 12D, 10 rats were killed respectively. The serum ALT, AST, total bilirubin (total bilirubin, TBil) were detected respectively. The liver index was calculated and the normal pathological changes of liver tissue were observed to determine the appropriate time to cause obvious liver injury. And the mice liver tissue two aldehyde (malondialdehyde, MDA), glutathione peroxidase (glutathione) was detected. Peroxidase (GSH-Px), to explore the mechanism of liver injury induced by Xanthii.
[results]
(1) the effect of different doses of xanthate Decoction on the serum ALT, AST and liver index of mice: compared with the blank group, the decoction of xanthate had significant influence on the serum ALT, AST and liver index of mice (P0.05). The difference of ALT between the high, middle and low dosage groups was 22, the higher the dose of the xanthate, the higher the ALT, and the dosage of the drug. There was positive correlation (P 0.05); there was significant difference in AST between low and high dose groups (P 0.05); there was no significant difference in liver index among the three groups (P 0.05).
(2) the effect of different doses of xanthate Decoction on the histomorphology of liver in mice: there was no obvious liver injury in the low dose group; in the high dose group, the liver injury was obvious, especially in the high dose group. The low dose xanthate decoction had no obvious effect on the mice liver cells (P0.005), high dose and medium dose. There was a significant difference between the group and the blank group (P0.005).
(3) the effect of high dose xanthate Decoction on the serum ALT, AST, TBil and liver index of mice at different time: 6D, the serum ALT, AST, TBil and liver index in the group 12D mice increased significantly, and there was significant statistical significance (P0.05) compared with the blank group (P0.05), but there was no significant difference between the two groups (P0.05).
(4) the effect of high dose xanthate Decoction on the histomorphology of liver in different time: 6D, group 12D mice had obvious liver tissue damage. The semi quantitative analysis of liver cell degeneration, high dose of xanthate Decoction 6D, 12D and blank group had significant statistical significance (P0.005), but there was no significant statistical significance between the two groups (P0.00 5).
(5) the effect of high dose of xanthate Decoction on MDA and GSH-Px in liver tissue of mice: compared with the blank group, the effect of high dose of xanthate Decoction on the level of MDA and GSH-Px in liver tissues of mice was not significant (P0.05), and the effect of high dose xanthate Decoction on the level of MDA and GSH-Px in liver tissues of mice was not significant (P0.05).
[Conclusion] (1) (1) the application of high dose (240g. Kg~ (-1)) xanthate Decoction to 6D can cause obvious liver damage in mice. (2) free radical lipid peroxidation may not be involved in liver injury induced by xanthate decoction, but it still needs to be further determined in the future experiment.
【學位授予單位】：河南中醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R-332;R259

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