CAJ | 학술논문

目的：观察透骨消痛胶囊对膝骨关节炎大鼠软骨内质网应激的影响，探讨透骨消痛胶囊治疗骨关节炎的可能机制。方法：将30只清洁级SD大鼠随机分为正常对照组，模型对照组，透骨消痛胶囊高、中、低剂量组，每组6只。除正常对照组外，其余各组采用质量分数为4%的木瓜蛋白酶注射建立大鼠膝骨关节炎模型。给药8周后，收集大鼠右侧股骨髁和胫骨平台，光镜检查软骨组织的形态学变化，利用原位末端标记法（TdT-mediated dUTP nick-end labeling,TUNEL）检测软骨细胞凋亡情况，免疫组化检测软骨组织内质网应激蛋白激酶（PKR-like ER kinase,PERK）、真核启动因子2α（eukaryotic translation initiation fac-tor 2α,eIF2α）、转录活化因子4（activating transcription factor 4,ATF4）、免疫球蛋白结合蛋白（immunoglobulin binding protein,Bip）、生长抑制 DNA 损伤基因153（growth arrest and DNA-damage-inducible gene 153, GADD153）、软骨细胞功能基因Ⅱ型胶原蛋白（Collage Ⅱ）和转录因子 SOX-9蛋白的表达。结果：透骨消痛胶囊对大鼠骨关节炎模型关节软骨的大体外观及 HE 染色均有明显改善，TUNEL 结果显示其能够降低软骨细胞凋亡指数（P <0.01），免疫组化结果显示透骨消痛胶囊较模型对照组能够下调 PERK、eIF2α、ATF4、Bip 及 GADD153蛋白表达，上调软骨细胞功能基因 Collage Ⅱ和 SOX-9的蛋白表达（P <0.05或 P <0.01）。结论：透骨消痛胶囊可通过抑制内质网应激的信号转导，减少软骨细胞的凋亡数目，改善软骨细胞形态，促进软骨细胞代谢及软骨修复，以维持软骨结构的相对完整，从而延缓关节软骨退变。
목적：관찰투골소통효낭대슬골관절염대서연골내질망응격적영향，탐토투골소통효낭치료골관절염적가능궤제。방법：장30지청길급SD대서수궤분위정상대조조，모형대조조，투골소통효낭고、중、저제량조，매조6지。제정상대조조외，기여각조채용질량분수위4%적목과단백매주사건립대서슬골관절염모형。급약8주후，수집대서우측고골과화경골평태，광경검사연골조직적형태학변화，이용원위말단표기법（TdT-mediated dUTP nick-end labeling,TUNEL）검측연골세포조망정황，면역조화검측연골조직내질망응격단백격매（PKR-like ER kinase,PERK）、진핵계동인자2α（eukaryotic translation initiation fac-tor 2α,eIF2α）、전록활화인자4（activating transcription factor 4,ATF4）、면역구단백결합단백（immunoglobulin binding protein,Bip）、생장억제 DNA 손상기인153（growth arrest and DNA-damage-inducible gene 153, GADD153）、연골세포공능기인Ⅱ형효원단백（Collage Ⅱ）화전록인자 SOX-9단백적표체。결과：투골소통효낭대대서골관절염모형관절연골적대체외관급 HE 염색균유명현개선，TUNEL 결과현시기능구강저연골세포조망지수（P <0.01），면역조화결과현시투골소통효낭교모형대조조능구하조 PERK、eIF2α、ATF4、Bip 급 GADD153단백표체，상조연골세포공능기인 Collage Ⅱ화 SOX-9적단백표체（P <0.05혹 P <0.01）。결론：투골소통효낭가통과억제내질망응격적신호전도，감소연골세포적조망수목，개선연골세포형태，촉진연골세포대사급연골수복，이유지연골결구적상대완정，종이연완관절연골퇴변。
[ABSTRACT] Objective:To observe the effect of Tougu Xiaotong Capsule (透骨消痛胶囊 ,TXC) on cartilage endoplasmic reticulum stress in rats with knee osteoarthritis in order to study its possible mechanism of treating osteoarthritis.Methods:Thirty clean SD rats were randomly divided into a normal control group,a model control group,and high,medium and low dose groups of TXC (HTXC group,MTXC group and LTXC group), 6 rats in each group.Except for the normal control group,the rest groups were given injections of 4% papain to establish rat models of knee osteoarthritis.After 8 weeks of medication,right lateral thighs and tibial plateaus of rats were collected to detect the morphological changes of cartilage tissue with light microscope.TUNEL (TdT-mediated UTP nick-end labeling) was used to detect chondrocyte apoptosis. Immunohistochemisty was used to detect the expressions of PERK (PKR-like ER kinase),eIF2α (eukaryotic translation initiation factor 2α),ATF4 (activating transcription factor 4),Bip (immunoglobulin binding protein),GADD153 (growth arrest and DNA-damage-inducible gene 153),Collage Ⅱ and transcription factor SOX-9.Results:TXC could significantly improve the general appearance and HE staining of articular cartilage of rat models.The results of TUNEL showed the decrease of chondrocyte apoptosis index (P < 0.01).Immunohistochemistry results showed the down-regulation of the expression of PERK,eIF2α,ATF4,Bip and GADD153 and the up-regulation of the expression of Collage Ⅱ and SOX-9 (P < 0.05 or P < 0.01).Conclusion:TXC,by way of inhibiting endoplasmic reticulum stress signal transduction,can reduce the number of chondrocyte apoptosis,improve the morphology of chondrocytes,promote the metabolism of chondrocytes and cartilage repair,and maintain relatively intact cartilage structure,to delay the degeneration of articular cartilage.