机构地区:[1]山东省中医药研究院中药药理研究所(药理实验中心),山东济南250014 [2]齐鲁工业大学(山东省科学院)山东省分析测试中心,山东济南250014 [3]山东中医药大学附属医院(第一临床学院),山东济南250014
出 处:《中国药物警戒》2024年第3期313-318,共6页Chinese Journal of Pharmacovigilance
基 金:中央本级重大增减支项目“名贵中药资源可持续利用能力建设项目”(2060302);国家自然科学基金资助项目(81704029);山东省自然科学基金联合基金重点资助项目(ZR2022LZY007);山东省中医药高层次人才培育项目(鲁卫人才字[2023]37号);齐鲁卫生与健康杰出青年人才资助项目(鲁卫人才字[2020]3号);山东省中医药科技项目(Z-2022098T)。
摘 要:目的比较枯芩、条芩提取物对湿热型溃疡性结肠炎(UC)大鼠模型的药效学差异。方法50只健康SD大鼠随机分为5组:正常组、模型组、枯芩组、条芩组和美莎拉嗪组,每组10只。采用高脂高糖饲料喂养+高度白酒灌胃+5%葡聚糖硫酸钠(DSS)联合诱导法,建立湿热型UC大鼠模型;各组分别于造模第1天开始灌胃给药,枯芩组、条芩组给药剂量均为5.25 g·kg^(-1)·d^(-1),美沙拉嗪组给药剂量为0.266 g·kg^(-1)·d^(-1),正常组、模型组灌服等体积生理盐水。连续给药28 d。观察大鼠一般情况;评价大鼠体质量变化和疾病活动指数(DAI)评分;称取大鼠结肠质量,量取结肠长度,并计算结肠单位长度质量;进行大鼠结肠组织HE染色和PAS染色,观察大鼠结肠组织病理学变化;Elisa法检测大鼠血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、转化生长因子-β_(1)(TGF-β_(1))炎症因子水平。结果与正常组比较,模型组大鼠的体质量显著降低,结肠长度显著缩短,DAI评分、结肠质量、结肠单位长度质量和血清IL-6、TNF-α、IL-1β水平均显著增加,TGF-β_(1)水平显著降低(P<0.01);结肠组织上皮层发生脱落,边缘散乱,隐窝不清晰,黏膜层有水肿,炎症细胞浸润且入侵黏膜下层,肠腺紊乱。与模型组比较,枯芩组、条芩组、美沙拉嗪组大鼠上述指标和相关症状均有明显改善(P<0.05,P<0.01);与枯芩组比较,条芩组、美沙拉嗪组在增加结肠单位长度质量、降低DAI评分、改善炎症因子水平方面均优于枯芩组(P<0.05或P<0.01)。结论枯芩、条芩提取物对湿热型UC大鼠均有较好的改善作用,且条芩优于枯芩。Objective To observe and compare the pharmacodynamics of extracts from Pith-decayed and Pith-nodecayed products of Scutellariae Radix on rats with damp-heat ulcerative colitis(UC).Methods Fifty healthy SD rats were randomly divided into 5 groups:normal group,model group,Pith-decayed products of Scutellariae Radix group,Pithnodecayed products of Scutellariae Radix group and mesalazine group,with 10 rats in each group.The damp-heat UC rat model was established by the combination of high-fat and high-sugar diet+high-liquor administration+5%dextran sodium sulfate(DSS).Each group was given intragastric administration on the first day of modeling,respectively.The dosage of Pith-decayed products group and Pith-nodecayed products group was 5.25 g·kg^(-1)·d^(-1),and that of mesalazine group was 0.266 g·kg^(-1)·d^(-1).Normal group and model group were given equal volume of normal saline.The drug was administered continuously for 28 days.The general condition of rats was observed.The change of body mass and the score of disease activity index(DAI)were evaluated.The colonic mass of rats was measured,the colonic length was measured,and the colonic mass per unit length was calculated.HE staining and PAS staining were performed to observe the histopathological changes of rat colon.Serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and transforming growth factor-β_(1)(TGF-β_(1))were detected by Elisa.Results Compared with normal group,body mass and colon length of rats in model group were significantly decreased,DAI score,colon mass,colon mass per unit length and serum levels of IL-6,TNF-αand IL-1βwere significantly increased,and TGF-β_(1)level was significantly decreased(P<0.01).The upper layer of colon tissue was exfoliated,the margins were scattered,the crypts were unclear,the mucosal layer was edema,inflammatory cells infiltrated and invaded the submucosa,and the intestinal glands were disturbed.Compared with model group,the above indexes and related symptoms were significant
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