辛伐他汀对胶原诱导关节炎大鼠的治疗机制探索.pdf

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1、58TianjinMedJ,Jan2014,Vol42No1*辛伐他汀对胶原诱导关节炎大鼠的治疗机制探索1212王友莲杨明峰尚可皮慧【摘要】目的以胶原诱导关节炎（CIA）大鼠为模型，观察辛伐他汀对其血清细胞因子及滑膜组织天冬氨酸蛋白水解酶-3（Caspase-3）表达的影响，探索辛伐他汀治疗类风湿关节炎的可能机制。方法使用牛Ⅱ型胶原建立CIA模型，将造模成功的大鼠（16只）均分为模型组及药物组，未造模者（7只）为对照组。药物组用2.0mg/（kg·d）灌胃，对照组和模型组用无菌注射用水5mL/（kg·d）灌胃。记录大鼠

2、关节炎评分（AI）和足趾容积，每周1次；初次免疫后第42天，眼内眦取血采用ELISA法检测各组血清肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6水平，处死大鼠取后肢踝关节进行HE染色，并用免疫组织化学检测滑膜组织Caspase-3表达。结果药物组和模型组AI在初次免疫后21d开始下降，35d后药物组均低于模型组（均P＜0.05）。2组足趾容积于初次免疫14d后缓慢下降，但仍明显高于对照组；35、42d时药物组均低于模型组（均P＜0.05）。初次免疫后42d，药物组TNF-α和IL-6水平均低于模型组，高于对照组（均

3、P＜0.05）。药物组较模型组踝关节滑膜组织增生明显减轻，仅有少量炎细胞浸润，Caspase-3的表达明显上调。结论辛伐他汀可明显抑制CIA大鼠血清TNF-α、IL-6的分泌，上调滑膜组织Caspase-3的表达及减轻滑膜组织增生。【关键词】辛伐他汀；关节炎,类风湿；白细胞介素6；肿瘤坏死因子α；半胱氨酸天冬氨酸蛋白酶3【中图分类号】R593【文献标识码】A【DOI】10.3969/j.issn.0253-9896.2014.01.018TherapeuticMechanismofSimvastatinonCollag

4、enInducedArthritisinRatsWANGYoulian1,YANGMingfeng2,SHANGKe1,PIHui21DepartmentofRheumatologyandImmunology,thePeople’sHospitalinJiangxiProvince,Nanchang330006,China;2MedicalCollegeofNanchangUniversity[Abstract]ObjectiveToevaluatetherapeuticeffectsofsimvastatinonse

5、rumexpressionsofcytokinesandsynovialtissueasparticprotease-3(Caspase-3)incollageninducedarthritis(CIA)inrats,andthemechanismthereof.MethodsTheratmodelofCIAwasestablishedbyinjectingbovineⅡcollagen.Sixteenmodelratswererandomlydividedintotwogroups:CIAmodelgroup(ste

6、rilewater5mL·kg-1·d-1bygavage)andsimvastatingroup(2.0mg·kg-1·d-1bygavage).Sevennormalratswereincludedincontrolgroup(sterilewater5mL·kg-1·d-1bygavage).Thearthritisindex(AI)andhindpawvol⁃umeswererecordedonceaweek.Theserumlevelsofcytokine,tumornecrosisfactor(TNF)-α

7、andinterleukin(IL)-6weremeasuredbyELISA42daysaftertheinitialimmunization.TheexpressionofCaspase-3inanklesynovialtissuewasdetect⁃edbyimmunohistochemicalmethod,andpathologicalresultsofHEstaininginratanklewerecomparedbetweenthreegroups.ResultsValuesofAIweredecrease

8、donthe24-doftheinitialimmunizationinsimvastatingroupandCIAmodelgroup,whichwassignificantlydecreasedonthe35-doftheinitialimmunizationinsimvastatingroupthanthatofCIAmod