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甲氨蝶呤联合双氯芬酸钠治疗关节炎模型大鼠的微环境变化 被引量:4
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作者 牛梓晗 冉新建 +4 位作者 麦伍拉尼·马木提 潘传鹏 何东航 任聪改 徐琦 《中国组织工程研究》 CAS 北大核心 2018年第32期5163-5168,共6页
背景:类风湿关节炎是以小关节疼痛肿胀及晨僵为主要临床表现的自身免疫性疾病,目前药物治疗主要通过非类固醇抗炎药联合使用改善病情抗风湿药物,但其药物对T细胞亚群平衡的影响及其机制目前尚不清楚。目的:探讨甲氨蝶呤联合双氯芬酸钠... 背景:类风湿关节炎是以小关节疼痛肿胀及晨僵为主要临床表现的自身免疫性疾病,目前药物治疗主要通过非类固醇抗炎药联合使用改善病情抗风湿药物,但其药物对T细胞亚群平衡的影响及其机制目前尚不清楚。目的:探讨甲氨蝶呤联合双氯芬酸钠治疗胶原诱导性关节炎(CIA)大鼠对Th17/Treg细胞平衡的影响及其作用机制。方法:建立雄性Wistar大鼠胶原诱导性关节炎模型,随机分为空白组、模型组、甲氨蝶呤组、双氯芬酸钠组、甲氨蝶呤联合双氯芬酸钠组(联合用药组)、阳性对照组。通过每周评定关节炎指数、测量足趾肿胀程度判断造模成功。药物治疗4周后取材,酶联免疫吸附实验检测外周血中白细胞介素10、转化生长因子β等细胞因子表达情况;流式细胞术检测脾脏Th17及Treg细胞的比例变化情况;RT-PCR法分别检测脾脏中Th17、Treg细胞的转录因子ROR-γt及Foxp3的mRNA表达。结果与结论:(1)药物治疗后,甲氨蝶呤组、双氯芬酸钠组、联合用药组与模型组比较,各治疗组均可改善大鼠一般状况及足趾肿胀程度、降低关节炎指数评分、减少炎症细胞浸润、抑制转录因子ROR-γt调控Th17细胞分化、调控转录因子Foxp3诱导CD4^+CD25+Foxp3^+Treg高分化,从而恢复Treg/Th17比例平衡,改善胶原诱导性关节炎大鼠关节炎症状,各组间平均灰度值差异有显著性意义(P <0.05);(2)联合组关节炎指数下降趋势更明显,且关节炎症状轻于其他造模组;双氯芬酸钠组能上调模型组大鼠外周血白细胞介素10、白细胞介素6表达,甲氨蝶呤组下调转化生长因子β水平占优势,联合用药组能显著上调模型组血清白细胞介素6、白细胞介素10水平,下调转化生长因子β表达;联合用药组能有效上调模型组Treg/Th17比例,显著抑制转录因子Foxp3及ROR-γt表达;(3)结果提示甲氨蝶呤联合双氯芬酸钠治疗具有协同效应,为治疗类风湿关节炎提供理论基础。 展开更多
关键词 胶原诱导性关节炎 甲氨蝶呤 双氯芬酸钠 调节性T细胞 TH17细胞 组织构建主题词:关节炎 甲氨蝶呤 TH17细胞 T淋巴细胞 细胞因子类 组织工程 关节炎 甲氨蝶呤 TH17细胞 T淋巴细胞 细胞因子类 组织工程
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The influence of OCT1 gene polymorphisms on the metformin response in Uygur patients with glucose metabolism disorder
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作者 WANG Tao YI Tao-cun +11 位作者 WANG Ye WANG Zhi-hong WANH Chang-hui MAO Xin-min ran xin-jian HU Meng-yin GE Wen-ning ZHANG Min-fang XIE Zi-jing LI Shi-qiang LAN Yi LI Lin-lin 《新疆医科大学学报》 CAS 2010年第10期1175-1180,共6页
Objective To determine the effects of genetic variation in the organic cation transporter 1(OCT1)on the short-term responses of the antidiabetic drug,metformin.Method A total of 22 patients recruited with type 2 diabe... Objective To determine the effects of genetic variation in the organic cation transporter 1(OCT1)on the short-term responses of the antidiabetic drug,metformin.Method A total of 22 patients recruited with type 2 diabetes or IFG were treated with metformin(2 000 mg/day)for 1 week.The patients were screened from Second Jikun hospital and Kashidonglu community medicine service,Urumqi,China and their surrounding districts.To examine the effects of metformin on plasma glucose,total cholesterol,low-density lipoprotein-cholesterol,high-density lipoprotein-cholesterol and triglyceride in relation with R61C,G465R and 420 del variants of OCT1(gene encoding organic cation transporter 1,mainly locating in liver,which is metformin's major target)in subjects.In all,R61C,G465R and 420del of OCT1 gene were examined using DNA extracted from whole blood and PCR-RFLP.Data concerning with gene and metformin treatment were handled by t-test.Result After metformin treatment,there were increases both in FPG and LDL(P=0.011and P=0.013 respectively).To divide all participants into mutant and wild groups,according to the polymorphisms of R61C,G465R and 420 del respectively,as well as carriers with one of the mutant genotypes at least and carriers with none of the mutant sites.Analysis was made to compared FPG,Chol,TG,and LDL and HDL between carriers of wild genotypes and carriers of other genotypes showed no statistic significance both before the metformin treatment and after the treatment.The same is the case with changes of FPG,Chol,TG,and LDL and HDL of wild genotype carriers and variant genotype carriers,except of LDL changes(P=0.05)in patients grouped by G465R polymorphisms and TG changes(P=0.03)in subjects differed by 420del genotypes.Conclusion In this study,it is suggested that OCT1 gene polymorphisms have little contribution to the clinical efficacy of blood glucose control by metformin among Uygur people with type 2 diabetes or IFG,but it may have possible relationship with the clinical efficacy on fat metabolism by metformin. 展开更多
关键词 OCT1基因 基因治疗 疗效
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