Abstract
Objective To investigate the mechanism of peiminine(PEI)affects pain and cartilage injury in rats with knee osteoarthritis(KOA)by regulating the peroxisome proliferat or-activated receptor gamma(PPARγ)/cellular sloan kettering institute(c-SKI)signaling pathway through a disintegrin and metalloproteinase with thrombospondin motifs 5(AD AMTS-5).Methods The KOA model was established in rats by intra-articular injection of sodium iodoacetate.The rats were divided into control group,model group,experimental group(intraperitoneal injection of 3.5 mg·kg-1 PEI)and ADAMTS-5 overexpression group(tail vein injection of oe-ADAMTS-5 plasmid).The pain threshold of rats was measured using the mechanical stimulation method;the pathological injury of the rat knee joint was examined by hematoxylin-eosin(HE)staining;the protein levels of ADAMTS-5,matrix metalloproteinase(MMP)-3,MMP-13 and proteins in the PPARγ/c-SKI signaling pathway in rat knee joint tissues were detected by Western blot;the protein level of collagen type Ⅱ alpha 1 chain(Col2α1)in rat knee joint tissues was determined by immunohistochemistry;the levels of inflammatory factors in rat serum were measured using corresponding commercial kits.Results The pain thresholds in control group,model group and experimental group were(19.15±2.87),(7.10±1.03)and(13.69±1.27)g,respectively;the relative expression levels of ADAMTS-5 were 1.00±0.16,1.77±0.21 and 1.35±0.18,respectively;Col2α1 levels in control,model,experimental,and ADAMTS-5 overexpression groups were 1.00±0.10,0.28±0.04,0.76±0.13 and 0.58±0.06,respectively;the relative expression levels of MMP-3 were 1.00±0.15,2.11±0.36,1.62±0.22 and 1.83±0.25,respectively;the relative expression levels of MMP-13 were 1.00±0.18,1.98±0.28,1.27±0.16 and 1.45±0.19,respectively;the tumor necrosis factor-alpha(TNF-α)levels were(62.74±6.93),(159.37±26.40),(98.08±14.09)and(124.43±17.79)pg·mL-1,respectively;the interleukin(IL)-4 levels were(75.62±11.54),(19.56±2.59),(53.28±6.34)and(41.67±5.31)pg·mL-1,respectively;IL-6 levels were(42.65±9.77),(133.84±13.22),(84.19±11.71)and(105.24±18.19)pg·mL-1,respectively;IL-10 levels were(98.06±24.50),(23.42±10.61),(64.72±20.96)and(38.09±12.86)pg·mL-1,respectively;the relative expression levels of PPARγ were 1.00±0.13,0.39±0.07,0.73±0.09 and 0.51±0.08,respectively;the relative expression levels of c-SKI were 1.00±0.17,0.32±0.05,0.86±0.15 and 0.44±0.09,respectively.The above indicators in model group were statistically significantly different from those in control group,those in experimental group were statistically significantly different from those in model group,and those in ADAMTS5 overexpression group were statistically significantly different from those in experimental group(all P＜0.05).Conclusion PEI inhibits inflammatory cytokine levels,alleviates bone fibrosis,and improves bone injury in KOA rats,thereby relieving joint pain,possibly by downregulating ADAMTS-5 expression to activate the PPARγ/c-SKI signaling pathway.关键词
贝母素乙/膝骨关节炎/含血小板蛋白结合基序的解聚蛋白样金属蛋白酶5/过氧化物酶体增殖物激活受体γ/细胞型禽肉瘤病毒癌基因同源物c-SKI信号通路/软骨损伤Key words
peiminine/knee osteoarthritis/disintegrin and metalloproteinase with thrombospondin motifs 5/peroxisome proliferator-activated receptor gamma/cellular sloan kettering institute signaling pathway/cartilage injury分类
医药卫生
