卡比孜胶囊对硫酸葡聚糖钠诱导的溃疡性结肠炎大鼠的药效学研究  

Pharmacodynamic study of Kabizi capsules on ulcerative colitis induced by dextran sulfate sodium in rats

作　　者：霍仕霞 祖力皮卡尔·吾斯曼 张兰兰 康雨彤 斯拉甫·艾白 李治建 杨雪[5] 邢建国[1,6] HUO Shi-xia;ZULIPIKAER Wu-si-man;ZHANG Lan-lan;KANG Yu-tong;SILAFU Ai-bai;LI Zhi-jian;YANG Xue;XING Jian-guo(School of Pharmacy,Xinjiang Medical University Urumqi 830011,Xinjiang Uygur Autonomous Region,China;Uygur Medical Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830049,Xinjiang Uygur Autonomous Region,China;Uygur Medicine Research Institute of Xinjiang Uygur Autonomous Region,Urumqi 830049,Xinjiang Uygur Autonomous Region,China;Bingtuan Food and Drug Evaluation and Verification Center,Urumqi 830037,Xinjiang Uygur Autonomous Region,China;Chongqing Academy of Chinese Materia Medica,Chongqing 400000,China;Medicine Research Institute of Xinjiang Uygur Autonomous Region,Urumqi 830002,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830011 [2]新疆维吾尔自治区维吾尔医医院,新疆乌鲁木齐830049 [3]新疆维吾尔自治区维吾尔医药研究所,新疆乌鲁木齐830049 [4]兵团食品药品审评核查中心,新疆乌鲁木齐830037 [5]重庆市中药研究院,重庆400000 [6]新疆维吾尔自治区药物研究所,新疆乌鲁木齐830002

出　　处：《中国临床药理学杂志》2023年第10期1461-1465,共5页The Chinese Journal of Clinical Pharmacology

基　　金：新疆维吾尔自治区重大科技专项基金资助项目(2016A03005);天山英才基金资助项目(2022TSYCCX0021,2022TSYCLJ009);中医药传承与创新“百千万”人才工程(岐黄工程)-青年岐黄学者基金资助项目。

摘　　要：目的探究卡比孜胶囊(SLZ)对溃疡性结肠炎(UC)所引起炎症、病理损伤及免疫反应的缓解作用。方法将大鼠用完全随机法分为正常对照组、模型组、卡比孜胶囊低、中、高剂量组(1.08、2.16、4.32 g·kg^(-1)卡比孜胶囊)和美沙拉嗪组(0.4 g·kg^(-1)美沙拉嗪)。自由饮用5%硫酸葡聚糖钠(DSS)造模液复制UC大鼠模型,造模成功后,按1 mL·100 g^(-1)的剂量灌胃给予相应的药物,其中正常对照组与模型组灌胃1 mL·100 g^(-1)纯净水。各组每天给药1次,连续7 d。用疾病活动指数(DAI)评分、结肠组织病理学观察大鼠结肠,用酶联免疫吸附试验法测定相关因子含量;用免疫组化法检测结肠组织含有CARD的凋亡相关斑点样蛋白、含半胱氨酸的天冬氨酸蛋白水解酶前体1、含半胱氨酸的天冬氨酸蛋白水解酶1、NOD样受体蛋白3(NLRP3)的表达水平。结果正常对照组、模型组、卡比孜胶囊高剂量组和美沙拉嗪实验组的血清白细胞介素-1表达量分别为(51.90±7.70)、(65.50±8.10)、(53.00±5.20)和(54.20±5.30)ng·L^(-1);白细胞介素-6表达量分别为(39.90±11.20)、(60.90±12.90)、(45.60±10.70)和(43.60±6.70)ng·L^(-1);超氧化物歧化酶表达量分别为(17.50±1.90)、(10.80±2.20)、(14.30±2.30)和(14.50±3.20)pg·mL^(-1),肿瘤坏死因子α表达量分别为(215.00±39)、(308.00±41.00)、(229.00±45.00)和(226.00±27.00)ng·L^(-1);NLRP3蛋白相对表达水平分别为0.60±0.02、0.74±0.02、0.62±0.01和0.63±0.02。正常对照组,卡比孜胶囊高剂量组和美沙拉嗪组的上述指标与模型组比较,差异均有统计学意义(P<0.05,P<0.01)。结论卡比孜胶囊可通过下调NLRP3炎性小体通路,从而改善DSS诱导的UC的炎症反应。Objective To investigate the alleviating effects of Kabizi capsules(SLZ)on the inflammation,pathological damage and immune response caused by ulcerative colitis(UC).Methods The rats were divided into control group,model group,SLZ-L,-M,-H groups(1.08,2.16,4.32 g·kg^(-1)SLZ)and mesalazine group(0.4 g·kg^(-1)mesalazine)by complete randomization method.UC rat model was replicated by drinking 5%sodium dextran sulfate(DSS)freely.After successful modeling,the corresponding drugs were administered by gavage at a dose of 1 mL·100 g^(-1),with the control group and the model group receiving 1 mL·100 g^(-1)of pure water.Each group was administered once a day for 7 d.The rat colon was observed by disease activity index(DAI)and colon histopathology,and the content of relevant factors was measured by enzyme-linked immunosorbent assay;the expression levels of apoptosis-associated speck-like protein containing a CARD(ASC),pro-cysteinyl aspartate specific proteinase 1,cysteinyl aspartate specific proteinase 1 and NOD-like receptor protein 3(NLRP3)in colon tissues were detected by immunohistochemistry.Results The serum levels of interleukin-1 in control group,model group,SLZ-H group and mesalazine group were(51.90±7.70),(65.50±8.10),(53.00±5.20)and(54.20±5.30)ng·L^(-1),respectively;interleukin-6 were(39.90±11.20),(60.90±12.90),(45.60±10.70)and(43.60±6.70)ng·L^(-1),respectively;superoxide dismutase were(17.50±1.90),(10.80±2.20),(14.30±2.30)and(14.50±3.20)pg·mL^(-1),respectively;tumor necrosis factor-αwere(215.00±39),(308.00±41.00),(229.00±45.00)and(226.00±27.00)ng·L^(-1),respectively;the relative expression levels of NLRP3 protein were 0.60±0.02,0.74±0.02,0.62±0.01 and 0.63±0.02,respectively.Compared with the model group,the above indexes in the control group,SLZ-H group and the mesalazine group were significantly different(P<0.05,P<0.01).Conclusion Kabizi capsules can improve the inflammatory response of DSS induced UC by reducing the NLRP3 inflammasome pathway.

关 键 词：卡比孜胶囊 葡聚糖硫酸钠 溃疡性结肠炎 炎症反应 

分 类 号：R28[医药卫生—中药学]