解酒饮对小鼠胃黏膜及急性四氯化碳肝损保护作用的药效学研究

发布时间：2018-05-09 00:32

本文选题：解酒饮 + 四氯化碳　；参考：《广西医科大学》2017年硕士论文

【摘要】：目的:研究解酒饮对四氯化碳(CCl_4)所致小鼠急性肝损伤的保护作用,同时研究解酒饮对酒精所致小鼠急性胃黏膜损伤的保护作用,并对其作用机制进行探讨,为进一步研究提供理论依据。方法:1、解酒饮对CCl_4所致小鼠急性肝损伤的保护作用。采用CCl_4制备小鼠急性肝损伤模型。将小鼠随机分为6组,每组10只:正常组、对照药联苯双酯组(150mg/kg)、模型组(0.3%CCl_4腹腔注射)和解酒饮低、中、高剂量组。解酒饮低、中、高剂量组分别按分别给6.25g/kg、12.5g/kg、25g/kg的解酒饮灌胃。造模12h后,比较各组的肝脏指数,并对肝组织进行组织形态学检查。采用全自动生化仪测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、血清白蛋白(ALB)、血清球蛋白(GLB)、血清总蛋白(TP)血清总蛋白的水平。取肝组织匀浆测定丙二醛(MDA)含量、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)的水平。此外,免疫组化方法检测肝脏锰型超氧化物歧化酶(Mn SOD)、B细胞淋巴瘤-2(Bcl-2)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的表达情况。采用荧光PCR法检测肝组织人核因子E2相关因子2(Nrf2)、SOD的基因表达水平。2.解酒饮对酒精所致小鼠急性胃黏膜损伤的保护作用。将60小鼠随机分为分为6组,每组10只:正常组、对照药硫糖铝咀嚼片组(600mg/kg)、模型组和解酒饮低、中、高剂量组。解酒饮低、中、高剂量组分别按分别给6.25g/kg、12.5g/kg、25g/kg的解酒饮灌胃。除正常组外,其余各组给予10ml/kg 95%乙醇灌胃造模。对各组小鼠的胃黏膜损伤和组织病理学进行检查。取胃黏膜组织匀浆测定一氧化氮(NO)、内皮素-1(ET-1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和前列腺素E2(PGE2)的含量。结果1.解酒饮降低CCl_4诱导的急性肝损伤小鼠血清升高的ALT、AST水平(P0.05)。解酒饮高剂量组降低肝匀浆升高的MDA水平,同时升高肝匀浆中的SOD和GSH酶活性(P0.05),改善肝组织的病理形态。免疫组化结果显示,高剂量组解酒饮可以上调Mn SOD、Bcl-2表达水平,下调Caspase-3表达水平。解酒饮对肝组织Nrf2、SOD的表达含量无明显影响。2.模型组小鼠胃黏膜出现明显出血、糜烂,点片状溃疡。与模型组比较,解酒饮中、高剂量组可明显降低小鼠胃水肿指数(P0.01)、胃黏膜损伤指数(P0.05或P0.01),降低胃黏膜ET-1水平(P0.05或P0.01)、降低胃黏膜TNF-α和IL-6含量(P0.05)。解酒饮高剂量组可升高胃黏膜NO水平(P0.05)。解酒饮对胃黏膜PGE2含量无明显影响(P0.05)。病理组织检查发现解酒饮可减少胃黏膜的脱落和炎细胞浸润。结论解酒饮可能通过提高肝脏抗氧化能力,抑制肝细胞凋亡,对小鼠急性CCl_4肝损伤有一定的保护作用。12.5g/kg、25g/kg剂量的解酒饮可通过改善胃黏膜血液循环,并减轻胃黏膜的炎性损伤,对小鼠急性胃黏膜损伤有保护作用。
[Abstract]:Objective: to study the protective effect of Jiejiu decoction on acute liver injury induced by CCl4 (CCl4) in mice, and to study the protective effect of Jiejiu decoction on acute gastric mucosal injury induced by alcohol in mice, and to explore its mechanism. To provide theoretical basis for further research. Methods: 1, jiedu Yin had protective effect on acute liver injury induced by CCl_4 in mice. The acute liver injury model of mice was established by CCl_4. Mice were randomly divided into 6 groups with 10 rats in each group: normal group, control group with 150 mg / kg of diphenyl ester, model group (0.3l_4 intraperitoneal injection) and low, medium and high dosage groups. In the low, medium and high dosage groups, 6.25 g / kg of alcohol was given 12.5 g / kg / kg or 25g / kg, respectively. After 12 hours, the liver index of each group was compared, and the liver tissue was examined by histomorphology. Serum alanine aminotransferase (alt), alanine aminotransferase (AST), serum albumin (Alb), serum globulin (GLB), serum total protein (TPTP) were measured by automatic biochemical instrument. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were measured in liver homogenate. In addition, immunohistochemical method was used to detect the expression of hepatic manganese superoxide dismutase (Mn-SODS-B cell lymphoma) -2pBcl-2and cysteine aspartate protease (Caspase-3). The expression level of sod in liver tissue was detected by fluorescence PCR method. Protective effect of Jiejiu Yin on Acute gastric mucosa injury induced by Alcohol in mice. 60 mice were randomly divided into 6 groups with 10 rats in each group: normal group, control group, sucralfate chewable tablet group, 600 mg / kg group, model group, low, medium and high dosage groups. In the low, medium and high dosage groups, 6.25 g / kg of alcohol was given 12.5 g / kg / kg or 25g / kg, respectively. In addition to the normal group, the rest groups were given 10ml/kg 95% ethanol intragastric perfusion model. Gastric mucosal injury and histopathology of mice in each group were examined. The contents of nitric oxide (no), endothelin-1 (et 1), tumor necrosis factor- 伪 (TNF- 伪), interleukin-6 (IL-6) and prostaglandin E _ 2 (PGE _ 2) were measured in gastric mucosa homogenate. Result 1. Jiejiuyin decreased serum alt level of acute liver injury mice induced by CCl_4 (P 0.05). The high dose group of Jiejiuyin decreased the level of MDA in liver homogenate and increased the activities of SOD and GSH in liver homogenate (P0.05), which improved the pathological morphology of liver tissue. Immunohistochemical results showed that Jijiu Yin could up-regulate the expression of Bcl-2 and down-regulate the expression of Caspase-3 in high dose group. Jiejiu Yin had no significant effect on the expression of SOD in liver tissue. In the model group, there were obvious bleeding, erosion and patchy ulcer in the gastric mucosa of mice. Compared with the model group, the high dose group could significantly reduce the gastric edema index (P 0.01), gastric mucosal injury index (P 0.05) or P 0.01 (P 0.01), ET-1 level (P 0.05 or P 0.01), and the contents of TNF- 伪 and IL-6 (P 0.05). The level of no in gastric mucosa was increased in high dose group of Jiejiu Yin (P 0.05). The content of PGE2 in gastric mucosa was not affected by Jiejiyin (P 0.05). Pathological examination showed that Jiejiu Yin could reduce gastric mucosal exfoliation and inflammatory cell infiltration. Conclusion Jiejiu decoction can improve the blood circulation of gastric mucosa and reduce the inflammatory injury of gastric mucosa by improving the anti-oxidation ability of liver and inhibiting the apoptosis of hepatocyte. It can protect mice from acute CCl_4 liver injury by 12.5 g / kg / kg and 25g / kg dose of Jiejiu Yin, which can improve the blood circulation of gastric mucosa and reduce the inflammatory injury of gastric mucosa. It has protective effect on acute gastric mucosal injury in mice.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5

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