滇结香花中5种化学成分对四氯化碳肝损伤小鼠的保护作用
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摘要
目的研究滇结香花中5种化合物对四氯化碳致小鼠肝损伤的保护作用及其作用机制。方法用四氯化碳诱导化学性肝损伤小鼠模型,随机分为空白组、模型组、阳性对照组、紫云英苷低、高剂量组(ZL、ZH)、西瑞香素低、高剂量组(XL、XH)、结香苷C低、高剂量组(JL、JH)、水杨酸低、高剂量组(SL、SH)、银锻苷低、高剂量组(YL、YH)。测定血清中AST、ALT含量,肝组织中MDA、SOD水平;应用RT-PCR测定肝组织中IL-6、TNF-αmRNA的相对表达量;HE染色观察病理切片,研究该5种化合物的保肝作用及其可能的作用机制。结果与模型组相比,ZH、SH、JL、JH、XH、YH能够明显降低血清中ALT、AST含量,明显改善肝脏病理组织状况,各给药组均能明显降低肝组织中MDA,提高SOD含量;RT-PCR结果显示,除ZL组外,其他给药组均能明显抑制TNF-αmRNA表达,除YL、ZL、XL组外,其他给药组对IL-6 mRNA的相对表达量的影响均具有统计学意义。结论 ZH、SH、JL、JH、XH、YH对四氯化碳引起的小鼠肝损伤具有较好的保护作用,可能是通过调节小鼠的免疫功能,增强肝脏抗氧化能力,减少脂质过氧化物生成发挥作用。
Aim To study the protective effect of five different compounds from Edgeworthi gardneri Meissn on carbon tetrachloride(CCl_4)-induced liver injury in mice and the possible mechanisms.Methods The models of acute liver injury were induced by CCl_4 in rats, which were then randomized into blank group, model group, positive control group, porphyrin low and high dose group(ZL, ZH), daphnoretin low and high dose group(XL, XH), vanillin C low and high dose group(JL, JH), ortho-hydroxybenzoic acid low and high dose group(SL, SH), and silver forging glycoside low and high dose group(YL, YH).The serum activities of alanine aminotransferase(ALT), aspartate aminotransferase(AST), contents of MDA and SOD in liver tissue homogenate were determined. The relative mRNA expression of TNF-α, IL-6 in the GAPDH were detected by RT-PCR, and the pathological section of liver tissue of mice was observed. The protective effect and possible mechanism of the five compounds were studied.Results Compared with model group,ZH, SH, JL, JH, XH, YH groups had obviously low serum ALT and AST levels(P<0.05, P<0.01).Phillygenin effectively improved the tissue lesion of liver, and each drug group could significantly reduce MDA content and improve SOD content. The relative mRNA expression of TNF-α, except ZL, the other dosage groups had significantly inhibitory effects. Except YL,ZL,XL,there was statistically significant difference in the relative mRNA expression of IL-6( P<0.05,P<0.01). Conclusions ZH,SH,JL,JH,XH,YH dosage groups have protective effects on acute hepatic injury induced by CCl_4 in mice. The mechanism may involve regulating the immune function of mice,enhancing the antioxidant capacity of liver and reducing the lipid peroxides.
Aim To study the protective effect of five different compounds from Edgeworthi gardneri Meissn on carbon tetrachloride(CCl_4)-induced liver injury in mice and the possible mechanisms.Methods The models of acute liver injury were induced by CCl_4 in rats, which were then randomized into blank group, model group, positive control group, porphyrin low and high dose group(ZL, ZH), daphnoretin low and high dose group(XL, XH), vanillin C low and high dose group(JL, JH), ortho-hydroxybenzoic acid low and high dose group(SL, SH), and silver forging glycoside low and high dose group(YL, YH).The serum activities of alanine aminotransferase(ALT), aspartate aminotransferase(AST), contents of MDA and SOD in liver tissue homogenate were determined. The relative mRNA expression of TNF-α, IL-6 in the GAPDH were detected by RT-PCR, and the pathological section of liver tissue of mice was observed. The protective effect and possible mechanism of the five compounds were studied.Results Compared with model group,ZH, SH, JL, JH, XH, YH groups had obviously low serum ALT and AST levels(P<0.05, P<0.01).Phillygenin effectively improved the tissue lesion of liver, and each drug group could significantly reduce MDA content and improve SOD content. The relative mRNA expression of TNF-α, except ZL, the other dosage groups had significantly inhibitory effects. Except YL,ZL,XL,there was statistically significant difference in the relative mRNA expression of IL-6( P<0.05,P<0.01). Conclusions ZH,SH,JL,JH,XH,YH dosage groups have protective effects on acute hepatic injury induced by CCl_4 in mice. The mechanism may involve regulating the immune function of mice,enhancing the antioxidant capacity of liver and reducing the lipid peroxides.
引文
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[9] 李孟秋, 窦洁, 杜伟, 等. 雷公藤红素对小鼠的免疫抑制作用及其对IL-6 mRNA表达影响的研究[J]. 中国临床药理学与治疗学, 2008,13(2): 158-63. Li M Q, Dou J, Du W,et al. Effects of trepterine on the immunosuppression action and expression IL-6 mRNA in mice[J]. Chin J Clin Pharmacol Ther, 2008,13(2): 158-63.
[10] 朱继孝, 李雪溦, 魏春华, 等. 洪连对ANIT所致肝损伤小鼠的保护作用[J]. 中国实验方剂学杂志, 2017,23(4): 140-4. Zhu J X, Li X W, Wei C H, et al. Protective effect of Lagotidis Herba on ANIT-induced liver injury in mice[J]. Chin J Exp Tradit Med Formul, 2017, 23(4): 140-4.
[11] 何薇, 陈熙, 陶莉, 等. 维生素D缺乏对四氯化碳急性肝损伤过程肝脏炎症的影响[J]. 中华疾病控制杂志, 2014, 18(5): 405-10. He W , Chen X , Tao L, et al . Effects of vitamin D deficiency on hepatic inflammation during carbon tetrachloride-induced acute liver injury in mice[J]. Chin J Dis Control Prev, 2014, 18(5): 405-10.
[12] Zhang D G, Zhang C, Wang J X, et al. Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation[J]. Toxicol Appl Pharmacol, 2017, 314: 39-47.
[13] 韩旭, 徐骏权, 王宝来, 等. 细胞因子(IL-6、IL-10、TNF-α)在华支睾吸虫病肝功能损伤中作用的研究[J]. 中国微生态学杂志, 2015, 27(3) : 263-5, 271. Han X , Xu J Q , Wang B L , et al. Role of cytokines(IL-6,IL-10,TNF-α) in liver dysfunction patients with clonorchiasis sinensis[J]. Chin J Mic, 2015, 27(3): 263-5, 271.
[14] Zeng B, Su M, Chen Q, et al. Protective effect of a polysaccharide from Anoectochilus roxburghii against carbon tetrachloride-induced acute liver injury in mice[J]. J Ethnopharmacol, 2017, 200(2): 124-35.
[15] Zhang S L, You S P, Liu T, et al. Preventive effects of total flavonoids from Nymphaea candida on CCl4 induced acute liver injury in mice[J]. Nat Prod Res Devel, 2016, 28(12): 2017-20.
[2] 南彩云, 朱继孝, 魏春华, 等. 滇结香花不同提取部位对四氯化碳诱导小鼠肝损伤的影响[J]. 中药新药与临床药理, 2017, 28(4): 454-8. Nan C Y, Zhu J X, Wei C H, et al. The protective effects of different extracts from Edgeworthia gardneri Meissn on carbon tetrachloride-induced liver injury in mice[J].Tradit Chin Drug Res Clin Pharmacol, 2017, 28(4): 454-8.
[3] Lu C L, Zhu L, Piao J H, Jiang J G. Chemical compositions extracted from Wikstroemia indica and their multiple activities[J].Pharm Biol, 2012, 50(2):225-31.
[4] 张立,喻文进,刘慧琼,等. 西瑞香素抗炎抑菌作用的初步实验研究[J]. 中医药导报, 2012, 18(6): 72-3. Zhang L, Yu W J, Liu H Q, et al. Experimental study on the anti-inflammatory and antibacteerial effects of daphnoretin[J].Guid J Tradit Chin Med Pharm, 2012, 18(6): 72-3.
[5] Nurgun K,Esra K A. In vivo anti-inflammatory and antinociceptive activities of the extracts and chemical constituents of an endemic Turkish plant, Salsola grandis[J]. Rec Nat Prod,2016, 10(3): 369-79.
[6] Yan J Z,Tong S Q, Chu J J, et al. Preparative isolation and purification of syringin and edgeworoside C from Edgeworthia chrysantha Lindl by high-speed counter-current chromatography[J]. J Chromatogr, 2004, 1043(2): 329-32.
[7] 万君, 叶菊风, 叶俊, 等. 穿心莲内酯对小鼠急性四氯化碳肝损伤的保护作用[J]. 实用医学杂志, 2014, 30(14): 2204-7. Wan J,Ye J F, Ye J, et al. Role of andrographolide in protection of CCl4-induced acute liver injury in mice[J]. J Pract Med, 2014, 30(14): 2204-7.
[8] 朱继孝, 张红阳, 李雪溦, 等. 两种兔耳草对四氯化碳致肝损伤小鼠保护作用的比较研究[J].中药新药与临床药理, 2016, 27(2): 210-4. Zhu J X , Zhang H Y ,Li X W, et al . Comparison of protective effects of two kinds of lagotises against mice liver injury induced by carbon tetrachloride[J].Tradit Chin Drug Res Clin Pharmacol, 2016, 27(2): 210-4.
[9] 李孟秋, 窦洁, 杜伟, 等. 雷公藤红素对小鼠的免疫抑制作用及其对IL-6 mRNA表达影响的研究[J]. 中国临床药理学与治疗学, 2008,13(2): 158-63. Li M Q, Dou J, Du W,et al. Effects of trepterine on the immunosuppression action and expression IL-6 mRNA in mice[J]. Chin J Clin Pharmacol Ther, 2008,13(2): 158-63.
[10] 朱继孝, 李雪溦, 魏春华, 等. 洪连对ANIT所致肝损伤小鼠的保护作用[J]. 中国实验方剂学杂志, 2017,23(4): 140-4. Zhu J X, Li X W, Wei C H, et al. Protective effect of Lagotidis Herba on ANIT-induced liver injury in mice[J]. Chin J Exp Tradit Med Formul, 2017, 23(4): 140-4.
[11] 何薇, 陈熙, 陶莉, 等. 维生素D缺乏对四氯化碳急性肝损伤过程肝脏炎症的影响[J]. 中华疾病控制杂志, 2014, 18(5): 405-10. He W , Chen X , Tao L, et al . Effects of vitamin D deficiency on hepatic inflammation during carbon tetrachloride-induced acute liver injury in mice[J]. Chin J Dis Control Prev, 2014, 18(5): 405-10.
[12] Zhang D G, Zhang C, Wang J X, et al. Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation[J]. Toxicol Appl Pharmacol, 2017, 314: 39-47.
[13] 韩旭, 徐骏权, 王宝来, 等. 细胞因子(IL-6、IL-10、TNF-α)在华支睾吸虫病肝功能损伤中作用的研究[J]. 中国微生态学杂志, 2015, 27(3) : 263-5, 271. Han X , Xu J Q , Wang B L , et al. Role of cytokines(IL-6,IL-10,TNF-α) in liver dysfunction patients with clonorchiasis sinensis[J]. Chin J Mic, 2015, 27(3): 263-5, 271.
[14] Zeng B, Su M, Chen Q, et al. Protective effect of a polysaccharide from Anoectochilus roxburghii against carbon tetrachloride-induced acute liver injury in mice[J]. J Ethnopharmacol, 2017, 200(2): 124-35.
[15] Zhang S L, You S P, Liu T, et al. Preventive effects of total flavonoids from Nymphaea candida on CCl4 induced acute liver injury in mice[J]. Nat Prod Res Devel, 2016, 28(12): 2017-20.