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解酒飲對小鼠胃黏膜及急性四氯化碳肝損保護(hù)作用的藥效學(xué)研究

發(fā)布時間:2018-05-09 00:32

  本文選題:解酒飲 + 四氯化碳 ; 參考:《廣西醫(yī)科大學(xué)》2017年碩士論文


【摘要】:目的:研究解酒飲對四氯化碳(CCl_4)所致小鼠急性肝損傷的保護(hù)作用,同時研究解酒飲對酒精所致小鼠急性胃黏膜損傷的保護(hù)作用,并對其作用機(jī)制進(jìn)行探討,為進(jìn)一步研究提供理論依據(jù)。方法:1、解酒飲對CCl_4所致小鼠急性肝損傷的保護(hù)作用。采用CCl_4制備小鼠急性肝損傷模型。將小鼠隨機(jī)分為6組,每組10只:正常組、對照藥聯(lián)苯雙酯組(150mg/kg)、模型組(0.3%CCl_4腹腔注射)和解酒飲低、中、高劑量組。解酒飲低、中、高劑量組分別按分別給6.25g/kg、12.5g/kg、25g/kg的解酒飲灌胃。造模12h后,比較各組的肝臟指數(shù),并對肝組織進(jìn)行組織形態(tài)學(xué)檢查。采用全自動生化儀測定血清谷丙轉(zhuǎn)氨酶(ALT)、谷草轉(zhuǎn)氨酶(AST)、血清白蛋白(ALB)、血清球蛋白(GLB)、血清總蛋白(TP)血清總蛋白的水平。取肝組織勻漿測定丙二醛(MDA)含量、超氧化物歧化酶(SOD)和還原型谷胱甘肽(GSH)的水平。此外,免疫組化方法檢測肝臟錳型超氧化物歧化酶(Mn SOD)、B細(xì)胞淋巴瘤-2(Bcl-2)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的表達(dá)情況。采用熒光PCR法檢測肝組織人核因子E2相關(guān)因子2(Nrf2)、SOD的基因表達(dá)水平。2.解酒飲對酒精所致小鼠急性胃黏膜損傷的保護(hù)作用。將60小鼠隨機(jī)分為分為6組,每組10只:正常組、對照藥硫糖鋁咀嚼片組(600mg/kg)、模型組和解酒飲低、中、高劑量組。解酒飲低、中、高劑量組分別按分別給6.25g/kg、12.5g/kg、25g/kg的解酒飲灌胃。除正常組外,其余各組給予10ml/kg 95%乙醇灌胃造模。對各組小鼠的胃黏膜損傷和組織病理學(xué)進(jìn)行檢查。取胃黏膜組織勻漿測定一氧化氮(NO)、內(nèi)皮素-1(ET-1)、腫瘤壞死因子-α(TNF-α)、白細(xì)胞介素-6(IL-6)和前列腺素E2(PGE2)的含量。結(jié)果1.解酒飲降低CCl_4誘導(dǎo)的急性肝損傷小鼠血清升高的ALT、AST水平(P0.05)。解酒飲高劑量組降低肝勻漿升高的MDA水平,同時升高肝勻漿中的SOD和GSH酶活性(P0.05),改善肝組織的病理形態(tài)。免疫組化結(jié)果顯示,高劑量組解酒飲可以上調(diào)Mn SOD、Bcl-2表達(dá)水平,下調(diào)Caspase-3表達(dá)水平。解酒飲對肝組織Nrf2、SOD的表達(dá)含量無明顯影響。2.模型組小鼠胃黏膜出現(xiàn)明顯出血、糜爛,點(diǎn)片狀潰瘍。與模型組比較,解酒飲中、高劑量組可明顯降低小鼠胃水腫指數(shù)(P0.01)、胃黏膜損傷指數(shù)(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)。解酒飲高劑量組可升高胃黏膜NO水平(P0.05)。解酒飲對胃黏膜PGE2含量無明顯影響(P0.05)。病理組織檢查發(fā)現(xiàn)解酒飲可減少胃黏膜的脫落和炎細(xì)胞浸潤。結(jié)論解酒飲可能通過提高肝臟抗氧化能力,抑制肝細(xì)胞凋亡,對小鼠急性CCl_4肝損傷有一定的保護(hù)作用。12.5g/kg、25g/kg劑量的解酒飲可通過改善胃黏膜血液循環(huán),并減輕胃黏膜的炎性損傷,對小鼠急性胃黏膜損傷有保護(hù)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- 偽 (TNF- 偽), 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- 偽 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.
【學(xué)位授予單位】:廣西醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R285.5

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