樹(shù)莓莖對(duì)藥物性肝損傷小鼠肝組織HMGB1、TLR4、NF-κB蛋白表達(dá)的影響
發(fā)布時(shí)間：2018-10-31 08:26
【摘要】：目的:研究樹(shù)莓莖抗藥物性肝損傷的作用及對(duì)肝組織中HMGB1、TLR4、NF-κB蛋白表達(dá)的影響,為樹(shù)莓莖的藥用開(kāi)發(fā)和臨床應(yīng)用提供實(shí)驗(yàn)依據(jù)。方法:72只健康雄性ICR小鼠,隨機(jī)分成6組,每組12只,即空白組、模型組、聯(lián)苯雙酯組、樹(shù)莓莖低劑量組、樹(shù)莓莖中劑量組、樹(shù)莓莖高劑量組。樹(shù)莓莖低、中、高劑量組分別給予樹(shù)莓莖水煎液提取物進(jìn)行灌胃,劑量分別為1.14g/kg、2.28g/kg、4.56g/kg,聯(lián)苯雙酯組給予聯(lián)苯雙酯混懸液0.15g/kg,空白組、模型組給予等體積的生理鹽水,給藥體積為20mL/kg。每日灌胃一次,連續(xù)四周。末次給藥1小時(shí)后,除空白組以外,其余各組ICR小鼠給予對(duì)乙酰氨基酚500mg/kg腹腔注射進(jìn)行造模,并觀察小鼠一般狀態(tài),禁食不禁水。造模24小時(shí)后小鼠眼球取血,檢測(cè)小鼠血清中ALT、AST的水平;取一部分肝臟用于HE染色并觀察其病理變化;ELISA法測(cè)定小鼠肝組織IL-1β、TNF-α的含量;免疫組織化學(xué)方法測(cè)定小鼠肝組織中HMGB1、TLR4、NF-κB蛋白的表達(dá)情況。結(jié)果:與空白組相比較,模型組小鼠血清中ALT、AST水平明顯升高,差異具有顯著性,有統(tǒng)計(jì)學(xué)意義(P0.01);與模型組相比較,樹(shù)莓莖高、中、低劑量組能不同程度的降低藥物性肝損傷小鼠血清中ALT、AST的水平,有顯著性差異,具有統(tǒng)計(jì)學(xué)意義(P0.01);HE染色結(jié)果可見(jiàn)樹(shù)莓莖高、中劑量組明顯減輕對(duì)乙酰氨基酚誘導(dǎo)小鼠肝細(xì)胞的腫脹程度和炎性細(xì)胞浸潤(rùn)的壞死面積;ELISA法檢測(cè)結(jié)果發(fā)現(xiàn)樹(shù)莓莖可降低小鼠肝組織IL-1β、TNF-α的含量(P0.01,P0.05);免疫組化檢測(cè)結(jié)果發(fā)現(xiàn)樹(shù)莓莖可降低小鼠肝組織中HMGB1、TLR4、NF-κB蛋白的表達(dá)(P0.01,P0.05)。結(jié)論:樹(shù)莓莖可通過(guò)抑制小鼠肝組織中HMGB1、TLR4、NF-κB蛋白的表達(dá),調(diào)控炎癥細(xì)胞因子的水平,起到抗藥物性肝損傷的作用。
[Abstract]:Objective: to study the effects of raspberry stem on drug-induced liver injury and the expression of HMGB1,TLR4,NF- 魏 B protein in liver tissue, and to provide experimental evidence for the medicinal development and clinical application of raspberry stem. Methods: 72 healthy male ICR mice were randomly divided into 6 groups with 12 in each group: blank group, model group, biphenyl diester group, low dose group of raspberry stem, middle dose group of stem of raspberry, high dose group of stem of raspberry. The low, middle and high doses of raspberry stem extract were given by gavage, the dose was 1.14 g / kg ~ (2. 28) g 路kg ~ (-1) 路kg ~ (-1), the biphenyl diester group was given 0.15 g / kg / kg biphenyl diester suspension, and the blank group was given biphenyl diester suspension 0.15 g / kg, respectively. The model group was given the same volume of normal saline and 20 mL / kg of saline. Gavage once a day for four weeks. One hour after the last administration, the other ICR mice were given paracetamol 500mg/kg intraperitoneally to model the mice except the blank group. The general state of the mice was observed and the water was fasted. After 24 hours of model, blood was taken from eyeball of mice to detect the level of ALT,AST in serum, part of liver was used for HE staining and pathological changes were observed, content of IL-1 尾 and TNF- 偽 in liver tissue of mice was determined by ELISA method. The expression of HMGB1,TLR4,NF- 魏 B protein in mouse liver was detected by immunohistochemical method. Results: compared with the blank group, the serum ALT,AST level in the model group was significantly higher than that in the blank group (P0.01). Compared with the model group, the Raspberry stem height, medium and low dose group can reduce the serum ALT,AST level of the drug-induced liver injury mice in varying degrees, there is significant difference (P0.01); The results of HE staining showed that the stem of raspberry was high, and the swelling degree of hepatocytes induced by acetaminophen and the necrotic area of inflammatory cells were significantly reduced in middle dose group. The results of ELISA assay showed that the stem of raspberry could reduce the contents of IL-1 尾 and TNF- 偽 in liver tissue of mice (P 0.01 P 0.05). The results of immunohistochemistry showed that the stem of raspberry could reduce the expression of HMGB1,TLR4,NF- 魏 B protein in liver tissue of mice (P0.01P05). Conclusion: the stem of raspberry can inhibit the expression of HMGB1,TLR4,NF- 魏 B protein and regulate the level of inflammatory cytokines in the liver tissue of mice.
【學(xué)位授予單位】：黑龍江中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R285.5
[Abstract]:Objective: to study the effects of raspberry stem on drug-induced liver injury and the expression of HMGB1,TLR4,NF- 魏 B protein in liver tissue, and to provide experimental evidence for the medicinal development and clinical application of raspberry stem. Methods: 72 healthy male ICR mice were randomly divided into 6 groups with 12 in each group: blank group, model group, biphenyl diester group, low dose group of raspberry stem, middle dose group of stem of raspberry, high dose group of stem of raspberry. The low, middle and high doses of raspberry stem extract were given by gavage, the dose was 1.14 g / kg ~ (2. 28) g 路kg ~ (-1) 路kg ~ (-1), the biphenyl diester group was given 0.15 g / kg / kg biphenyl diester suspension, and the blank group was given biphenyl diester suspension 0.15 g / kg, respectively. The model group was given the same volume of normal saline and 20 mL / kg of saline. Gavage once a day for four weeks. One hour after the last administration, the other ICR mice were given paracetamol 500mg/kg intraperitoneally to model the mice except the blank group. The general state of the mice was observed and the water was fasted. After 24 hours of model, blood was taken from eyeball of mice to detect the level of ALT,AST in serum, part of liver was used for HE staining and pathological changes were observed, content of IL-1 尾 and TNF- 偽 in liver tissue of mice was determined by ELISA method. The expression of HMGB1,TLR4,NF- 魏 B protein in mouse liver was detected by immunohistochemical method. Results: compared with the blank group, the serum ALT,AST level in the model group was significantly higher than that in the blank group (P0.01). Compared with the model group, the Raspberry stem height, medium and low dose group can reduce the serum ALT,AST level of the drug-induced liver injury mice in varying degrees, there is significant difference (P0.01); The results of HE staining showed that the stem of raspberry was high, and the swelling degree of hepatocytes induced by acetaminophen and the necrotic area of inflammatory cells were significantly reduced in middle dose group. The results of ELISA assay showed that the stem of raspberry could reduce the contents of IL-1 尾 and TNF- 偽 in liver tissue of mice (P 0.01 P 0.05). The results of immunohistochemistry showed that the stem of raspberry could reduce the expression of HMGB1,TLR4,NF- 魏 B protein in liver tissue of mice (P0.01P05). Conclusion: the stem of raspberry can inhibit the expression of HMGB1,TLR4,NF- 魏 B protein and regulate the level of inflammatory cytokines in the liver tissue of mice.
【學(xué)位授予單位】：黑龍江中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R285.5
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