紫地榆提取物对慢性溃疡性结肠炎大鼠的治疗作用
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摘要
目的考察紫地榆乙酸乙酯提取物(EAEG)对慢性溃疡性结肠炎(UC)大鼠的治疗作用。方法采用免疫造模法制备UC大鼠模型。将大鼠随机分为空白组,模型组,柳氮磺胺吡啶组(SASP,100 mg·kg~(-1)),EAEG低、中、高剂量组(50、100、200 mg·kg~(-1)),灌胃给药(10 mL·kg~(-1)),每日1次,连续给药15 d。观察大鼠一般情况,并测定大鼠体质量指数、结肠湿质量指数及胸腺、脾脏、肝脏脏器指数;HE染色观察结肠、脾脏组织病理学变化;采用分光光度法测定结肠组织和血清中丙二醛(MDA)、超氧化物歧化酶(SOD)及髓过氧化物酶(MPO)活性;采用双抗体夹心ELISA法测定血清中肿瘤坏死因子α(TNF-α)、白介素6(IL-6)含量。结果与空白组比较,模型组大鼠的体质量指数、胸腺指数显著降低(P <0.01),结肠湿质量指数、脾脏指数及肝脏指数显著升高(P <0.01),血清中MDA、MPO、TNF-α、IL-6含量明显升高(P <0.01),SOD活性明显降低(P <0.01),结肠组织中MDA含量明显增加(P <0.01)。与模型组比较,EAEG高、低剂量组的体质量指数明显升高(P <0.05);EAEG中、低剂量组的结肠湿质量指数明显降低(P <0.05);EAEG各剂量组的脾脏指数均明显降低(P <0.05,P <0.01),EAEG高剂量组的肝脏指数明显降低(P <0.05),而对胸腺指数的影响不明显(P>0.05);EAEG高、中剂量组的结肠组织中MDA含量、血清中TNF-α含量明显降低(P <0.05,P <0.01);EAEG各剂量组的血清MPO、IL-6含量均明显降低(P <0.05,P <0.01);EAEG高剂量组血清中SOD活性明显增强(P <0.05)。模型组结肠黏膜有大量炎性细胞浸润,局部可见黏膜层完全脱落,出现组织坏死,EAEG高、中剂量组观察到局部肉芽组织的修复。结论 EAEG对UC大鼠有一定的治疗作用,可能与其提高机体抗氧化能力和降低TNF-α、IL-6等炎症因子表达有关。
Objective To investigate the effect of the ethyl acetate extracts from Geranium strictipes R. Knuth(EAEG) on the chronic ulcerative colitis(UC)in rats. Methods The ulcerative colitis rat models were established using immunological method. The animals were randomly divided into five groups:model group,low,middle and high dosage(50,100,200 mg·kg~(-1))of EAEG and the sulfasalazine(SASP)group(100 mg·kg~(-1)),which were for i.g. 15 days continuously. The change of general conditions of the rats is observed,the weight,colon,thymus,spleen and liver indexes were measured,and the pathological change of colon and spleen in rats were observed at the end of the experiment. Meanwhile,the content of malondialdehyde(MDA),the activities of myeloperoxidase(MPO)and superoxide dismutase(SOD)and in the colon tissues and serum were measured by spectrophotometry.In addition, the contents of the TNF-α, IL-6 in serum of rats were examined by ELISA. Results The weight indexes of rats in model group, SASP group and EAEG groups were declined(P < 0.01)compared with blank group. Compared with model group,the weight indexes of rats in EAEG high and low dose groups increased(P <0.05);the colon indexes of rats in EAEG medium and low dose groups decreased(P < 0.05);the spleen indexes of rats in all EAEG groups decreased(P < 0.05;P < 0.01);and the liver index of rats in high dose EAEG group decreased(P < 0.05)with no obvious effect on thymus index(P>0.05). The serum contents of MDA and TNF-α in rats of high and medium dose EAEG groups decreased(P < 0.05,P < 0.01). The serum contents of MPO and IL-6 in rats of all EAEG groups decreased(P < 0.05,P < 0.01),the MPO activities and contents of MDA of rats in all EAEG groups decreased(P < 0.05;P < 0.01). The activity of SOD in serum of rats in high dose EAEG group was enhanced(P < 0.05). In the model group the inflammatory cell infiltration, thorough colonic mucous membrane abscission, tissue mortification and focal ulceration appeared in the colon tissue; however, the local repair of granulation tissue for the damnification was observed in the high and medium EAEG groups' rats. Conclusion The results showed that the extracts from Geranium strictipes R. Knuth have certain effect on the UC and the potential mechanism may be that the extracts could improve the ability of anti-oxidation and decline the expression of TNF-αand IL-6.
Objective To investigate the effect of the ethyl acetate extracts from Geranium strictipes R. Knuth(EAEG) on the chronic ulcerative colitis(UC)in rats. Methods The ulcerative colitis rat models were established using immunological method. The animals were randomly divided into five groups:model group,low,middle and high dosage(50,100,200 mg·kg~(-1))of EAEG and the sulfasalazine(SASP)group(100 mg·kg~(-1)),which were for i.g. 15 days continuously. The change of general conditions of the rats is observed,the weight,colon,thymus,spleen and liver indexes were measured,and the pathological change of colon and spleen in rats were observed at the end of the experiment. Meanwhile,the content of malondialdehyde(MDA),the activities of myeloperoxidase(MPO)and superoxide dismutase(SOD)and in the colon tissues and serum were measured by spectrophotometry.In addition, the contents of the TNF-α, IL-6 in serum of rats were examined by ELISA. Results The weight indexes of rats in model group, SASP group and EAEG groups were declined(P < 0.01)compared with blank group. Compared with model group,the weight indexes of rats in EAEG high and low dose groups increased(P <0.05);the colon indexes of rats in EAEG medium and low dose groups decreased(P < 0.05);the spleen indexes of rats in all EAEG groups decreased(P < 0.05;P < 0.01);and the liver index of rats in high dose EAEG group decreased(P < 0.05)with no obvious effect on thymus index(P>0.05). The serum contents of MDA and TNF-α in rats of high and medium dose EAEG groups decreased(P < 0.05,P < 0.01). The serum contents of MPO and IL-6 in rats of all EAEG groups decreased(P < 0.05,P < 0.01),the MPO activities and contents of MDA of rats in all EAEG groups decreased(P < 0.05;P < 0.01). The activity of SOD in serum of rats in high dose EAEG group was enhanced(P < 0.05). In the model group the inflammatory cell infiltration, thorough colonic mucous membrane abscission, tissue mortification and focal ulceration appeared in the colon tissue; however, the local repair of granulation tissue for the damnification was observed in the high and medium EAEG groups' rats. Conclusion The results showed that the extracts from Geranium strictipes R. Knuth have certain effect on the UC and the potential mechanism may be that the extracts could improve the ability of anti-oxidation and decline the expression of TNF-αand IL-6.
引文
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[10]杨雷,李越,李艳霞,等.金丝桃苷对葡聚糖硫酸钠诱导小鼠结肠炎Nrf2/ARE信号通路的作用[J].胃肠病学和肝病学杂志,2017,26(11):1255-1257.
[11]赵益,赖小东,叶争荣,等.葛根芩连汤对溃疡性结肠炎模型大鼠抗氧化及抗炎的作用机制[J].中华中医药杂志,2016,31(5):1741-1745.
[12]周承志,姜楠,周从辉,等.复方苦参汤对溃疡性结肠炎模型大鼠的干预作用及作用机制研究[J].中国药师,2016,19(10):1816-1820.
[13]温如燕,罗霞,郑彦懿,等.大黄牡丹汤对葡聚糖硫酸钠诱导的溃疡性结肠炎小鼠的治疗作用[J].中药新药与临床药理,2016,27(5):649-654.
[14]金艳,钦丹萍,杨新艳,等.克痢痧胶囊抑制大鼠乙酸性结肠炎[J].中成药,2017,39(9):1789-1794.
[15]司海鹏,朱长乐,秦菲,等.中药经验方治疗溃疡性结肠炎不同时期TNF-α及IL-23的变化[J].世界中医药,2018,13(1):76-79.
[16]赵莉,石志敏,李雪青.补脾胃泻阴火升阳汤联合美沙拉嗪治疗溃疡性结肠炎患者疗效观察[J].中国实验方剂学杂志,2017,23(14):1-4.
[2]LIN X Y,LIN T H,YING Z S,et al.RIP3 deficiency exacerbates inflammation in dextran sodium sulfate-induced ulcerative colitis mice model[J].Cell Biochemistry&Function,2017,35(3):156-163.
[3]沈洪,刘智群,朱荃,等.清肠化湿方对溃疡性结肠NF-κB/Tolls通路的影响及其机制[J].中国中西医结合杂志,2013,33(9):1216-1220.
[4]康正祥,叶伟成,李嘉炎.肠安冲剂对实验性大鼠溃疡性结肠炎作用机理的研究[J].上海中医药大学学报,2001,15(2):46-48.
[5]云南省卫生局革命委员会.云南中草药[M].昆明:云南人民出版社,1971:796-797.
[6]全国中草药汇编编写组.全国中草药汇编(下册)[M].北京:人民卫生出版社,1983:624.
[7]金晴昊.复方老鹳草浸膏对大鼠溃疡性结肠炎的防治作用[D].延吉:延边大学,2006.
[8]魏伟,吴希美,李元建,等.药理实验方法学[M].4版.北京:人民卫生出版社,2010:1117-1118.
[9]郭利军,王晶,申元英,等.三种免疫血清制备方法的比较[J].大理学院学报,2004,3(5):7-8.
[10]杨雷,李越,李艳霞,等.金丝桃苷对葡聚糖硫酸钠诱导小鼠结肠炎Nrf2/ARE信号通路的作用[J].胃肠病学和肝病学杂志,2017,26(11):1255-1257.
[11]赵益,赖小东,叶争荣,等.葛根芩连汤对溃疡性结肠炎模型大鼠抗氧化及抗炎的作用机制[J].中华中医药杂志,2016,31(5):1741-1745.
[12]周承志,姜楠,周从辉,等.复方苦参汤对溃疡性结肠炎模型大鼠的干预作用及作用机制研究[J].中国药师,2016,19(10):1816-1820.
[13]温如燕,罗霞,郑彦懿,等.大黄牡丹汤对葡聚糖硫酸钠诱导的溃疡性结肠炎小鼠的治疗作用[J].中药新药与临床药理,2016,27(5):649-654.
[14]金艳,钦丹萍,杨新艳,等.克痢痧胶囊抑制大鼠乙酸性结肠炎[J].中成药,2017,39(9):1789-1794.
[15]司海鹏,朱长乐,秦菲,等.中药经验方治疗溃疡性结肠炎不同时期TNF-α及IL-23的变化[J].世界中医药,2018,13(1):76-79.
[16]赵莉,石志敏,李雪青.补脾胃泻阴火升阳汤联合美沙拉嗪治疗溃疡性结肠炎患者疗效观察[J].中国实验方剂学杂志,2017,23(14):1-4.