【摘要】 目的研究川芎嗪联合塞来昔布对早期膝骨关节炎大鼠的影响及其对脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）信号通路的影响。方法将SD大鼠随机分为假手术组、模型组、实验组和阳性对照组,每组12只;用改良Hulth’s法构建膝骨关节炎模型,假手术组只切开关节腔,不切断前交叉韧带,术后8周实验组灌胃川芎嗪50 mg·kg^-1+塞来昔布4 mg·kg^-1,阳性对照组灌胃塞来昔布4 mg·kg^-1,模型组和假手术组灌胃给予等体积0. 9%Na Cl溶液,每日1次,连续干预30 d。检测大鼠血浆中血管性血友病因子（v WF）和D-二聚体（D-D）水平;检测大鼠软骨组织中白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）表达量;以苏木精-伊红（HE）染色法观察大鼠关节软骨组织形态学变化,以蛋白免疫印迹（WB）法检测各组大鼠关节软骨组织中PI3K/AKT信号通路蛋白表达。结果假手术组、模型组、实验组和阳性对照组大鼠软骨组织IL-6分别为（78. 45±6. 59）,（148. 63±2. 74）,（89. 45±5. 63）,（96. 25±4. 52）pg·L^-1,IL-1β分别为（1. 32±0. 06）,（4. 56±0. 24）,（2. 15±0. 42）,（2. 52±0. 32） ng·L^-1;大鼠Mankin’s评分分别为（0. 25±0. 04）,（7. 52±0. 63）,（2. 56±0. 34）,（3. 52±0. 41）分;大鼠关节软骨组织中p-PI3K蛋白相对表达量分别为1. 52±0. 36,0. 33±0. 14,1. 25±0. 32,0. 96±0. 12,pAkt蛋白相对表达量分别为0. 98±0. 12,0. 48±0. 06,0. 79±0. 07,0. 62±0. 04,差异均有统计学意义（均P <0. 05）。结论川芎嗪联合塞来昔布可改善早期膝骨关节炎大鼠血液高凝状态,降低软骨组织炎性因子水平,可上调软骨组织中PI3K/AKT信号通路蛋白表达而起到较好的治疗作用。更多还原

【Abstract】 Objective To investigate the effects of ligustrazine combined with celecoxib on lipid inositol 3 kinase（ PI3K）/protein kinase B（ AKT） signaling pathway in early knee osteoarthritis rats. Methods SD rats were randomly divided into sham operation group,model group,test group and positive control group,12 rats in each group,modified Hulth’s method was used to construct knee osteoarthritis model. Eight weeks after operation,the test group was given orally ligustrazine 50 mg·kg^-1 and celecoxib 4 mg·kg^-1,positive control group was orally given celecoxib 4 mg · kg^-1,model group and sham operation group were orally given 0. 9% NaCl solution of equal volume once a day for 30 days continuously. The levels of D-dimer（ D-D） and von willebrand factor（ v WF） in rats plasma were detected,the expression of interleukin-6（ IL-6） and interleukin-1β（ IL-1β） in chondrocytes were detected,the morphological changes of articular cartilage were observed by hematoxylin and eosin（ HE） staining,and the expression of PI3K/AKT signal pathway protein in articular cartilage was detected by Western blot（ WB）. Results The levels of IL-6 in the cartilaginous tissue in sham operation group,model group,test group and positive control group were（ 78. 45 ± 6. 59）,（ 148. 63 ± 2. 74）,（ 89. 45 ± 5. 63）,（ 96. 25 ± 4. 52） pg·L^-1,the levels of IL-1β were（ 1. 32 ± 0. 06）,（ 4. 56 ± 0. 24）,（ 2. 15 ± 0. 42）,（ 2. 52 ± 0. 32） ng·L^-1; the Mankin’s scores of rats were0. 25 ± 0. 04,7. 52 ± 0. 63,2. 56 ± 0. 34,3. 52 ± 0. 41; the relative expression of p-PI3K protein in articular cartilage of rats were 1. 52 ± 0. 36,0. 33 ± 0. 14,1. 25 ± 0. 32,0. 96 ± 0. 12,the relative expression of p-Akt were0. 98 ± 0. 12,0. 48 ± 0. 06,0. 79 ± 0. 07,0. 62 ± 0. 04,all with statistical differences（ all P < 0. 05）. Conclusion Ligustrazine combined with celecoxib can improve blood hypercoa-gulability,decrease the level of inflammatory factors in cartilage tissue,and up-regulate the expression of PI3K/AKT signaling pathway protein in cartilage tissue and play a better therapeutic role in early knee osteoarthritis rats.更多还原