健骨方对兔膝骨关节炎软骨的影响及治疗膝骨关节炎的临床观察
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摘要
目的:观察健骨方对膝骨关节炎模型兔的关节软骨形态学与组织学改变、软骨细胞分泌基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-3(MMP-3)、特异性组织基质金属蛋白酶抑制因子(TIMP-1)、白细胞介素-1β(IL-1β)的作用及对软骨细胞凋亡指数(AI)与增殖指数(PI)的不同影响;健骨方治疗膝骨关节炎的临床疗效观察,为探讨中药疗效的作用机制及临床用药提供依据。
方法:实验研究:将35只新西兰兔随机分7组,正常对照组,模型对照组,补肾组,活血化瘀组,清热利湿组,祛风胜湿组,补肾活血解毒组,前两组给予生理盐水,后五组分别给予左归丸,失笑散,四妙散,豨桐丸,健骨方。饲养8周后大体观察关节结构一般表现,光镜下观察形态学变化并检测软骨、滑膜中MMP-1、MMP-3、TIMP-1、IL-1β的表达阳性情况,MMP-3、TIMP-1平均灰度的检测,软骨细胞的凋亡指数和增殖指数。临床观察:将60例膝骨关节炎患者随机分为试验组和对照组,试验组30例服用健骨方,对照组30例服用硫酸氨基葡萄糖,两组疗程均为6个月。
结果:实验研究:光镜下观察形态学变化:据Mankin’s评分标准,对光镜下关节软骨及滑膜的退变程度评分,模型对照组评分明显高于正常对照组(P<0.05),表明建模成功;健骨方组、失笑散组、豨桐丸组、四妙散组、左归丸组评分分别与模型对照组比较均有降低(P<0.05),表明以上各组可以通过降低评分来改善软骨病变;健骨方组评分分别与其他各中药组比较均有降低(P<0.05),表明健骨方组在降低评分改善软骨病变方面优于其他各中药组。光镜下观察组织学变化:左归丸组,失笑散组,四妙散组,豨桐丸组、健骨方组中关节软骨、滑膜中MMP-1、MMP-3、IL-1β阳性表达较模型对照组均降低,健骨方组降低较为明显;左归丸组,失笑散组,四妙散组,豨桐丸组、健骨方组中关节软骨、滑膜中TIMP-1阳性表达较模型对照组均有升高,健骨方组升高较为明显。软骨、滑膜中MMP-3平均灰度方面:模型对照组与正常对照组比较均数增高(P<0.05),表明建模成功;健骨方组、左归丸组、四妙散组、失笑散组、豨桐丸组分别与模型对照组比较均数降低(P<0.05),表明以上各组可以通过降低软骨细胞中MMP-3平均灰度来改善软骨病变;健骨方组分别与其他各中药组比较均数降低(P<0.05),表明健骨方组在降低软骨细胞中MMP-3平均灰度方面优于其他各中药组。软骨、滑膜中TIMP-1平均灰度方面:模型对照组与正常对照组比较均数增高(P<0.05),表明建模成功;健骨方组、左归丸组、四妙散组、失笑散组、豨桐丸组与模型对照组比较均数增高(P<0.05),表明以上各组可以通过增高软骨细胞中TIMP-1而改善软骨病变;健骨方组与其他各中药组比较均数增高(P<0.05),说明健骨方组在增高软骨细胞中TIMP-1平均灰度方面优于其他各中药组。软骨细胞的增殖指数方面:模型对照组与正常对照组比较均数降低(P<0.05),表明建模成功;健骨方组与模型对照组比较均数增高(P<0.05),表明健骨方可以通过刺激软骨细胞的增值而改善软骨病变;其他各中药组分别与模型对照组比较均数增高,但差异无统计学意义(P>0.05)。软骨细胞的凋亡指数方面:模型对照组与正常对照组比较均数增高(P<0.05),表明建模成功;健骨方组、失笑散组、豨桐丸组与模型对照组比较均数均有降低(P<0.05),表明以上各组可以降低软骨细胞凋亡指数来改善软骨病变;四妙散组、左归丸组与模型对照组比较均数降低,但差异无统计学意义(p>0.05);健骨方组分别与其他各中药组比较均数降低(P<0.05),表明健骨方组在降低软骨细胞凋亡指数方面明显优于其他各中药组。临床观察:治疗后,中医症候积分和病情轻重方面,试验组与对照组比较,差异有统计学意义(P<0.05),说明试验组在改善中医症候和病情轻重方面优于对照组;降低C反应蛋白(CRP)方面,两组组内比较,差异有统计学意义(P<0.05),组间比较,差异无统计学意义(P>0.05),说明在降低CRP方面两组疗效现当。
结论:实验研究显示健骨方能改善软骨及滑膜的退变程度计分,有效的降低关节软骨MMP-1、MMP-3、TIMP-1、IL-1β阳性表达和MMP-3平均灰度,降低软骨细胞的凋亡指数,升高软骨细胞的增殖指数和TIMP-1平均灰度来改善软骨病变,其具体作用机理有待于进一步探讨;临床观察显示健骨方治疗膝骨关节炎患者疗效肯定,并可以有效降低CRP。
Objective: To observe health bone with osteoarthritis of rabbit knee articular cartilage morphology and histological changes in cartilage cell secretion of matrix metalloproteinase -1 (MMP-1), matrix metalloproteinase -3 (MMP-3), specific matrix metalloproteinase inhibitor (TIMP-1), interleukin-1β(IL-1β) and the role of chondrocyte apoptosis index (AI) and value-added index (PI) of the different effects; Health Treatment of Knee Bone Clinical efficacy of arthritis, to investigate the mechanism of traditional Chinese medicines and provide the basis for clinical treatment.
Methods: Study: 35 New Zealand rabbits were randomly divided into 7 groups, normal control group, model control group, kidney group, blood circulation group, heat Lishi Group, chills wins wet group, kidney and blood detoxification group, the former two groups of saline, after the five groups were given ZuoguiWan Shixiaosan, four wonderful casual, Herba Tong pills, bone health side. Gross observation after 8 weeks the general performance of joint structure, the morphological changes observed under light microscope and to detect cartilage and synovial membrane in the MMP-1, MMP-3, TIMP-1, IL-1βexpression in positive cases, MMP-3, TIMP -1 average gray detection of chondrocyte apoptosis index and proliferation index. Clinical observation: 60 patients with knee osteoarthritis were randomly divided into test group and control group, experimental group of 30 patients taking healthy bone side, the control group of 30 patients taking glucosamine sulfate, were treated for 6 months.
Results: Study: morphological changes observed under light microscope: According to Mankin's score, optical microscopy of articular cartilage and synovial degeneration score, model control group scores were significantly higher than the control group (P <0.05), that modeling success; healthy bone side group Shixiaosan group, Herba Tong pill group, four wonderful powder group, scores were Zuoguiwan group compared with the control group were lower (P <0.05), showed that each group can be reduced more than score to improve cartilage lesions; Strengthening bone group scores were compared with other Chinese groups were lower (P <0.05), that group of healthy bone with cartilage lesions in the lower scores improved better than the other Chinese groups. Histological changes observed under light microscope: Zuoguiwan group Shixiaosan group, four wonderful powder group, Herba Tong pill group, the group Strengthening bone articular cartilage, synovial MMP-1, MMP-3, IL-1β-positive expression were lower than the model control group, bone health side were decreased more significantly; Zuoguiwan group Shixiaosan group, four wonderful powder group, Herba Tong pill group, the group health bone with articular cartilage, synovial TIMP-1 positive expression were higher than the model control group, bone health side group increased more significantly. Cartilage and synovial MMP-3 in the average gray areas: model control group and the normal control group mean increased (P <0.05), show that the model successfully; healthy bone side group Zuoguiwan group, four wonderful scattered groups Shixiaosan group, Herba Tong Wan group compared with the control group, respectively, the mean reduction (P <0.05), that the above groups by reducing MMP-3 in cartilage cells to improve cartilage lesions of the average gray; Strengthening bone group were compared with all the other reduce the number of Chinese groups (P <0.05), that group of healthy bone with cartilage cells in reducing MMP-3 is better than the other average gray Medicines. Cartilage and synovial TIMP-1 in the average gray areas: model control group and the normal control group mean increased (P <0.05), shows that successful modeling; healthy bone side group Zuoguiwan group, four wonderful scattered groups Shixiaosan group, Herba Tong Wan group compared with the control group mean increased (P <0.05), that the above groups can be increased TIMP-1 in cartilage cells to improve cartilage lesions; healthy bone with traditional Chinese medicine group and other groups mean increased (P <0.05), that group health bone with cartilage cells increased TIMP-1 is superior to the other average gray Medicines. Enhanced index of chondrocytes: the model group compared with the control group mean decreased (P <0.05), shows that successful modeling; Strengthening bone group and the model number of the control group were higher (P <0.05), showed that bone health party can add value by stimulating cartilage cells to improve cartilage lesions; other Chinese groups were compared with the control group mean increased, but the difference was not statistically significant (P> 0.05). Apoptotic index of chondrocytes: the model group compared with the control group mean increased (P <0.05), shows that successful modeling; healthy bone side group Shixiaosan group, Herba Tong Wan group compared with the control group mean were lower (P <0.05), that the above groups can reduce the apoptotic index of chondrocytes to improve cartilage lesions; four wonderful scattered groups Zuoguiwan group compared with the control group mean decreased, but the difference was not statistically significant ( p> 0.05); healthy bone with traditional Chinese medicine group were compared with the other numbers were lower (P <0.05), that group of healthy bone with the cartilage in the lower apoptotic index was superior to the other Chinese groups. Clinical observations: After treatment, TCM syndrome score and severity, the experimental group and control group, the difference was statistically significant (P <0.05), that the experimental group in improving symptoms and severity of traditional Chinese medicine is better than the control group; lower C reactive protein (CRP), the both groups, the difference was statistically significant (P <0.05), between the two groups, the difference was not statistically significant (P> 0.05), shows efficacy in reducing CRP is when the two groups.
Conclution: The study showed that bone health can only improve the degeneration of cartilage and synovial level score, effectively reduce the articular cartilage of MMP-1, MMP-3, TIMP-1, IL-1βexpression and MMP-3 mean gray and reduce the apoptotic index of chondrocytes, cartilage cells increased TIMP-1 value-added index and the average gray to improve the cartilage lesions, the specific mechanism remains to be further explored; clinical observation showed that bone health side effects treatment of knee osteoarthritis sure, and can reduce CRP.
方法:实验研究:将35只新西兰兔随机分7组,正常对照组,模型对照组,补肾组,活血化瘀组,清热利湿组,祛风胜湿组,补肾活血解毒组,前两组给予生理盐水,后五组分别给予左归丸,失笑散,四妙散,豨桐丸,健骨方。饲养8周后大体观察关节结构一般表现,光镜下观察形态学变化并检测软骨、滑膜中MMP-1、MMP-3、TIMP-1、IL-1β的表达阳性情况,MMP-3、TIMP-1平均灰度的检测,软骨细胞的凋亡指数和增殖指数。临床观察:将60例膝骨关节炎患者随机分为试验组和对照组,试验组30例服用健骨方,对照组30例服用硫酸氨基葡萄糖,两组疗程均为6个月。
结果:实验研究:光镜下观察形态学变化:据Mankin’s评分标准,对光镜下关节软骨及滑膜的退变程度评分,模型对照组评分明显高于正常对照组(P<0.05),表明建模成功;健骨方组、失笑散组、豨桐丸组、四妙散组、左归丸组评分分别与模型对照组比较均有降低(P<0.05),表明以上各组可以通过降低评分来改善软骨病变;健骨方组评分分别与其他各中药组比较均有降低(P<0.05),表明健骨方组在降低评分改善软骨病变方面优于其他各中药组。光镜下观察组织学变化:左归丸组,失笑散组,四妙散组,豨桐丸组、健骨方组中关节软骨、滑膜中MMP-1、MMP-3、IL-1β阳性表达较模型对照组均降低,健骨方组降低较为明显;左归丸组,失笑散组,四妙散组,豨桐丸组、健骨方组中关节软骨、滑膜中TIMP-1阳性表达较模型对照组均有升高,健骨方组升高较为明显。软骨、滑膜中MMP-3平均灰度方面:模型对照组与正常对照组比较均数增高(P<0.05),表明建模成功;健骨方组、左归丸组、四妙散组、失笑散组、豨桐丸组分别与模型对照组比较均数降低(P<0.05),表明以上各组可以通过降低软骨细胞中MMP-3平均灰度来改善软骨病变;健骨方组分别与其他各中药组比较均数降低(P<0.05),表明健骨方组在降低软骨细胞中MMP-3平均灰度方面优于其他各中药组。软骨、滑膜中TIMP-1平均灰度方面:模型对照组与正常对照组比较均数增高(P<0.05),表明建模成功;健骨方组、左归丸组、四妙散组、失笑散组、豨桐丸组与模型对照组比较均数增高(P<0.05),表明以上各组可以通过增高软骨细胞中TIMP-1而改善软骨病变;健骨方组与其他各中药组比较均数增高(P<0.05),说明健骨方组在增高软骨细胞中TIMP-1平均灰度方面优于其他各中药组。软骨细胞的增殖指数方面:模型对照组与正常对照组比较均数降低(P<0.05),表明建模成功;健骨方组与模型对照组比较均数增高(P<0.05),表明健骨方可以通过刺激软骨细胞的增值而改善软骨病变;其他各中药组分别与模型对照组比较均数增高,但差异无统计学意义(P>0.05)。软骨细胞的凋亡指数方面:模型对照组与正常对照组比较均数增高(P<0.05),表明建模成功;健骨方组、失笑散组、豨桐丸组与模型对照组比较均数均有降低(P<0.05),表明以上各组可以降低软骨细胞凋亡指数来改善软骨病变;四妙散组、左归丸组与模型对照组比较均数降低,但差异无统计学意义(p>0.05);健骨方组分别与其他各中药组比较均数降低(P<0.05),表明健骨方组在降低软骨细胞凋亡指数方面明显优于其他各中药组。临床观察:治疗后,中医症候积分和病情轻重方面,试验组与对照组比较,差异有统计学意义(P<0.05),说明试验组在改善中医症候和病情轻重方面优于对照组;降低C反应蛋白(CRP)方面,两组组内比较,差异有统计学意义(P<0.05),组间比较,差异无统计学意义(P>0.05),说明在降低CRP方面两组疗效现当。
结论:实验研究显示健骨方能改善软骨及滑膜的退变程度计分,有效的降低关节软骨MMP-1、MMP-3、TIMP-1、IL-1β阳性表达和MMP-3平均灰度,降低软骨细胞的凋亡指数,升高软骨细胞的增殖指数和TIMP-1平均灰度来改善软骨病变,其具体作用机理有待于进一步探讨;临床观察显示健骨方治疗膝骨关节炎患者疗效肯定,并可以有效降低CRP。
Objective: To observe health bone with osteoarthritis of rabbit knee articular cartilage morphology and histological changes in cartilage cell secretion of matrix metalloproteinase -1 (MMP-1), matrix metalloproteinase -3 (MMP-3), specific matrix metalloproteinase inhibitor (TIMP-1), interleukin-1β(IL-1β) and the role of chondrocyte apoptosis index (AI) and value-added index (PI) of the different effects; Health Treatment of Knee Bone Clinical efficacy of arthritis, to investigate the mechanism of traditional Chinese medicines and provide the basis for clinical treatment.
Methods: Study: 35 New Zealand rabbits were randomly divided into 7 groups, normal control group, model control group, kidney group, blood circulation group, heat Lishi Group, chills wins wet group, kidney and blood detoxification group, the former two groups of saline, after the five groups were given ZuoguiWan Shixiaosan, four wonderful casual, Herba Tong pills, bone health side. Gross observation after 8 weeks the general performance of joint structure, the morphological changes observed under light microscope and to detect cartilage and synovial membrane in the MMP-1, MMP-3, TIMP-1, IL-1βexpression in positive cases, MMP-3, TIMP -1 average gray detection of chondrocyte apoptosis index and proliferation index. Clinical observation: 60 patients with knee osteoarthritis were randomly divided into test group and control group, experimental group of 30 patients taking healthy bone side, the control group of 30 patients taking glucosamine sulfate, were treated for 6 months.
Results: Study: morphological changes observed under light microscope: According to Mankin's score, optical microscopy of articular cartilage and synovial degeneration score, model control group scores were significantly higher than the control group (P <0.05), that modeling success; healthy bone side group Shixiaosan group, Herba Tong pill group, four wonderful powder group, scores were Zuoguiwan group compared with the control group were lower (P <0.05), showed that each group can be reduced more than score to improve cartilage lesions; Strengthening bone group scores were compared with other Chinese groups were lower (P <0.05), that group of healthy bone with cartilage lesions in the lower scores improved better than the other Chinese groups. Histological changes observed under light microscope: Zuoguiwan group Shixiaosan group, four wonderful powder group, Herba Tong pill group, the group Strengthening bone articular cartilage, synovial MMP-1, MMP-3, IL-1β-positive expression were lower than the model control group, bone health side were decreased more significantly; Zuoguiwan group Shixiaosan group, four wonderful powder group, Herba Tong pill group, the group health bone with articular cartilage, synovial TIMP-1 positive expression were higher than the model control group, bone health side group increased more significantly. Cartilage and synovial MMP-3 in the average gray areas: model control group and the normal control group mean increased (P <0.05), show that the model successfully; healthy bone side group Zuoguiwan group, four wonderful scattered groups Shixiaosan group, Herba Tong Wan group compared with the control group, respectively, the mean reduction (P <0.05), that the above groups by reducing MMP-3 in cartilage cells to improve cartilage lesions of the average gray; Strengthening bone group were compared with all the other reduce the number of Chinese groups (P <0.05), that group of healthy bone with cartilage cells in reducing MMP-3 is better than the other average gray Medicines. Cartilage and synovial TIMP-1 in the average gray areas: model control group and the normal control group mean increased (P <0.05), shows that successful modeling; healthy bone side group Zuoguiwan group, four wonderful scattered groups Shixiaosan group, Herba Tong Wan group compared with the control group mean increased (P <0.05), that the above groups can be increased TIMP-1 in cartilage cells to improve cartilage lesions; healthy bone with traditional Chinese medicine group and other groups mean increased (P <0.05), that group health bone with cartilage cells increased TIMP-1 is superior to the other average gray Medicines. Enhanced index of chondrocytes: the model group compared with the control group mean decreased (P <0.05), shows that successful modeling; Strengthening bone group and the model number of the control group were higher (P <0.05), showed that bone health party can add value by stimulating cartilage cells to improve cartilage lesions; other Chinese groups were compared with the control group mean increased, but the difference was not statistically significant (P> 0.05). Apoptotic index of chondrocytes: the model group compared with the control group mean increased (P <0.05), shows that successful modeling; healthy bone side group Shixiaosan group, Herba Tong Wan group compared with the control group mean were lower (P <0.05), that the above groups can reduce the apoptotic index of chondrocytes to improve cartilage lesions; four wonderful scattered groups Zuoguiwan group compared with the control group mean decreased, but the difference was not statistically significant ( p> 0.05); healthy bone with traditional Chinese medicine group were compared with the other numbers were lower (P <0.05), that group of healthy bone with the cartilage in the lower apoptotic index was superior to the other Chinese groups. Clinical observations: After treatment, TCM syndrome score and severity, the experimental group and control group, the difference was statistically significant (P <0.05), that the experimental group in improving symptoms and severity of traditional Chinese medicine is better than the control group; lower C reactive protein (CRP), the both groups, the difference was statistically significant (P <0.05), between the two groups, the difference was not statistically significant (P> 0.05), shows efficacy in reducing CRP is when the two groups.
Conclution: The study showed that bone health can only improve the degeneration of cartilage and synovial level score, effectively reduce the articular cartilage of MMP-1, MMP-3, TIMP-1, IL-1βexpression and MMP-3 mean gray and reduce the apoptotic index of chondrocytes, cartilage cells increased TIMP-1 value-added index and the average gray to improve the cartilage lesions, the specific mechanism remains to be further explored; clinical observation showed that bone health side effects treatment of knee osteoarthritis sure, and can reduce CRP.
引文
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[9]诸丹虎.益气养血祛湿益肝方治疗慢性乙肝36例.中国医药指南杂志,2007 9:54
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[12]段冠清,蔡莹,沈慧.骨碎补总黄酮含药血清对大鼠成骨细胞AR mRNA表达的影响中医药导报,2010 ,16(2) :61-62
[13]纪莉连,范怡梅.土茯苓取物的抗细茵活性研究[J].生命科学研究,2010,6(1):84-87
[14]吴丽明,张敏.土茯苓中落新妇甙的利尿和镇痛作用.中药材,1995,18(12):627
[15]余庆阳,姚履渊,林红珍,等.严重创伤后的代谢反应与中药治疗的临床研究[J].中国中医骨伤科杂志,2000,8(2):18
[16]王怡,翁维良,刘剑刚,等.动物类活血化瘀药对血液流变性作用的比较研究[J].中药药理与临床,1997,13(3):1
[17]劳爱娜,桑圣民.常用中药基础研究(第五章)[M].北京高等教育出版社,2002,80-l12
[18]张团笑,牛彩琴,秦晓民.王不留行对家兔离体主动脉环张力的影响及其机制[J].中药药理与临床,2004,20(4):28-29
[19] Kosuge,Takuo.et al.Studies on bioactive substances in crude drug used for arthritic disease in traditional chinese medicine I.Isolation and identification of an anti inflammatory and analgesic prinaple from the root of angellica pubesedens maxim.ssswqqs Chem Pharm Bull.1985.33(12):5351
[20]卢永昌,张雪梅.独活抗氧化作用的研究.青海师专学报(教育科学),2004,5:74-76
[21]滞蔷,何开泽,等.JI J牛膝多糖的体外免疫活忡研究.已投应用环境物学报.
[22]王剑,付田,蒲蔷,何开泽.川牛膝多糖的体内免疫活性研究.张国林中药药理与临床,2007,23(6): 31-33
[23]赵兴梅,徐光忠,李建利,等.川牛膝和怀牛膝的现代药理研究概况.华西药学杂志,2004,19(3):205-207
[24]孙剑,陈朝蔚.阳和汤对兔骨关节炎软骨细胞中结缔组织生长因子表达的影响[J].中国中医骨伤科杂志,2009 ,17(3):56-57
[25]邓博,孙飞,祁开泽,等.复骨键骨片对兔膝关节骨性关节炎软骨细胞凋亡的影响[J].中医正骨,2008 ,9 (9) :15-16
[26]卢思俭,姜全心,王成.益肾为主对兔膝骨性关节炎模型软骨细胞凋亡的影响[J].山东中医药杂志,2006 ,25 (10) :696-698
[27]赵瑜,陈华燕,刘日光,等.补肾康膝方对家兔软骨细胞增殖与凋亡的影响陈述详.时珍国医国药,2008 ,19 (5) :1133-1134
[28]邹丹,全宏勋,胡群员.牛膝精对辐射小鼠造血干细胞增殖与分化的影响.四川中医,2003,21(7):16-17
[29]高晓燕,王大为,李发美,等.牛膝提取物对成骨样细胞增殖的作用.沈阳药科大学学报,2000,17(3):210-213
[30]孙奋勇,潘秋辉,洪岸.牛膝促进成细胞增殖的作用与机理研究. 2004,27(4):264-266
[31]王和鸣,余丹丹,汤亭亭,等.龟鹿二仙胶汤及其拆方对关节软骨细胞增殖的作用[J].中国中医骨伤科杂志, 2007, 15(7 ) :45-47
[32]舒谦,卿茂盛,曹亚飞,等.六味地黄汤含药血清对软骨细胞增殖、凋亡影响的体外实验研究[J].中国中医药科技, 2006, 13(4) : 217
[33]赵湘洪,陈宝兴,丁继华,等.骨碎补对实验性骨性关节炎的治疗作用.中药材,2004,27(4):264-266
[34] Gouze JN,Bordji K,Gulberti S ,et al. lnterleukin-1 beta down-regulates the expression of glucuronosyl transferase1,a key enzyme priming glycosaminoglycan biosynthesis:influence of glucosamine on interleukinl beta mediated effects in rat chondrocytes[J]arthritis Rheum,2001,44(2):351-360
[35] Héraud F, Héraud A , Harmand M F. Apop to sis inno rmal and o steoarth rit ic human art icular cart ilage [J ].A nn Rheum D is, 2000, 59 (12) : 959-965
[36]刘宝新,陈廖斌,汪辉,等.当归阿魏酸钠局部用药治疗骨关节炎的实验研究[J].中国矫形外科杂志,2008 ,16 (17) :1316-1318
[37]王玉彬,陈安民.基质金属蛋白酶家族在骨关节炎软骨组织中表达的研究.中国矫形外科杂志,2007,15(11):36-37
[38] Mehraban F,Lark MV,Ahmed FNetal.[J]. Osteoarthritis Cartilage,1998,6(4):286-294
[39]王毅,邢国胜.IL-1β诱导软骨细胞培养金属蛋白酶/金属蛋白酶抑制剂水平及药物对其影响.中华风湿病学杂志,2003,12(7):718-721
[40]杨坚,史晨辉.MMPs及相关细胞因子在骨性关节炎中的研究. 2009,31(5):448
[41]周晓莉.IL-1在骨关节炎发病及治疗应用中的研究现状.海南医学,2010,21(3):101-103
[42]国延军,牟成林.祛瘀通痹汤治疗原发性膝骨关节炎的临床研究,2009,24(3):21-22
[43]吴剑,鲍同柱.栀子对兔膝骨关节炎模型关节软骨病理改变及IL-1β表达的影响.第二军医大学学报,2009 ,30(3):329-331
[44] Gouze JN,Bordji K,Gulberti S ,et al. lnterleukin-1 beta down-regulates the expression of glucuronosyl transferase1,a key enzyme priming glycosaminoglycan biosynthesis:influence of glucosamine on interleukinl beta mediated effects in rat chondrocytes[J]arthritis Rheum,2001,44(2):351-360
[45] Spencer CM,Wilde MI. Drugs. 1997,53(1):98-106
[1]王玉彬,陈安民.基质金属蛋白酶家族在骨关节炎软骨组织中表达的研究.中国矫形外科杂志,2007,15(17):853-855
[2]刘志翔,张柳.基质金属蛋白酶和骨关节炎的研究进展.华北煤炭医学院学报,2007,9(3) :330-333
[3] Hulejova H , Baresova V , Klezl Z , et al . Increased level of cytokines and mat rix metalloproteinases in osteoart hritic sub2 chondral bone[J].Cytokine,2007,38(3) :151-156
[4] McCachren SS.Expression of metalloproteinases and metalloproteinasenhibitor in human arthritic synovium[J].Arthritis Rheum,1991,34:1085
[5]吕存贤,王维佳.膝骨关节炎病因病理研究及中医治疗概况.浙江中医学院学报,2005,29(1):82-83
[6]梁祖建,韩清民.“补肾活血方”对骨关节炎软骨保护的效应与机制研究.江苏中医药杂志,2009 ,41(3) :33-34
[7]杨坚,史晨辉.MMPs及相关细胞因子在骨性关节炎中的研究.农垦医学, 2009,31:448-451
[8]周晓莉.IL-1在骨关节炎发病及治疗应用中的研究现状.海南医学,2010,21(3):101-103
[9]江锋,陈巍膝.骨性关节炎患者关节滑液肿瘤坏死因子的表达及其临床意义.实用医学杂志,2010,26(2),246-247
[10]丁仁奎.膝关节退行性骨关节病与骨质疏松的相关关系研究.湖南医学,1997,14(6):323
[11]叶云,朱骏.骨质疏松与骨性关节炎关系的实验研究.浙江临床医学,2009,12(12):1287
[12]周凤鑫.组织血液灌注与微循环的病理生理(3)-血液流变性障碍[J].外科理论与实践,2008,13(1):附13-20.
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[16]胡建华,黄公怡,黄尚志,等.骨关节炎软骨细胞调控基因的研究[J].中华外科杂志,2000,38(4):266-286
[17]朱萱萱,支月芳,邱召娟,等.痛痹颗粒及拆方的含药血清对家兔软骨细胞增殖与凋亡的影响[J].实用中医内科学杂志,2006 ,20 (6) :603-604
[18]唐勇,姜杰,孟辉,等.补肾益气活血方对家兔软骨细胞凋亡和bcl-2mRNA表达的影响[J] .中国中医基础医学杂志,2006 ,12 (3) :174-175
[19]刘秋红.补肾活血法治疗膝骨关节炎42例.实用中医内科杂志,2009,23 (9):71-72
[2] Gouze JN,Bordji K,Gulberti S et al. lnterleukin-1 beta down-regulates the expression of glucuronosyl transferase1 ,a key enzyme priming glycosaminoglycan biosynthesis:influence of glucosamine on interleukinl beta mediated effects in rat chondrocytes[J]arthritis Rheum,2001,44(2):351-360
[3]刘谟震.MMP-12在类风湿关节炎中和骨性关节炎中的研究[J].医师进修杂志, 2004,27(6):23
[4] Lohmander LS,Hoerrner LA,Lark MWet al.Metalloproteinases,tissue inhibitor,and proteoglycan fragments in knee synovial fluid inhuman osteoarthritis.Arthritis Rheum,1993,36:181-189
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[6]郑筱萸.中药新药临床研究指导原则[M].中医药科技出版社,2002,5:180-184
[7]刘明伟.膝骨性关节炎临床用药体会.广西中医学院校报,2008:3
[8]宋康,骆仙芳,石亚杰,等.虎杖对肺纤维化大鼠Thl/Th2细胞因子干预作用的实验研究.中华中医药杂志(原中国医药学报), 2006,2l(12):781-783
[9]诸丹虎.益气养血祛湿益肝方治疗慢性乙肝36例.中国医药指南杂志,2007 9:54
[10]赵湘洪.中药通报.1987,12(10):4l
[11]丁继华.中国中医骨伤科杂志.1989,5(8):3
[12]段冠清,蔡莹,沈慧.骨碎补总黄酮含药血清对大鼠成骨细胞AR mRNA表达的影响中医药导报,2010 ,16(2) :61-62
[13]纪莉连,范怡梅.土茯苓取物的抗细茵活性研究[J].生命科学研究,2010,6(1):84-87
[14]吴丽明,张敏.土茯苓中落新妇甙的利尿和镇痛作用.中药材,1995,18(12):627
[15]余庆阳,姚履渊,林红珍,等.严重创伤后的代谢反应与中药治疗的临床研究[J].中国中医骨伤科杂志,2000,8(2):18
[16]王怡,翁维良,刘剑刚,等.动物类活血化瘀药对血液流变性作用的比较研究[J].中药药理与临床,1997,13(3):1
[17]劳爱娜,桑圣民.常用中药基础研究(第五章)[M].北京高等教育出版社,2002,80-l12
[18]张团笑,牛彩琴,秦晓民.王不留行对家兔离体主动脉环张力的影响及其机制[J].中药药理与临床,2004,20(4):28-29
[19] Kosuge,Takuo.et al.Studies on bioactive substances in crude drug used for arthritic disease in traditional chinese medicine I.Isolation and identification of an anti inflammatory and analgesic prinaple from the root of angellica pubesedens maxim.ssswqqs Chem Pharm Bull.1985.33(12):5351
[20]卢永昌,张雪梅.独活抗氧化作用的研究.青海师专学报(教育科学),2004,5:74-76
[21]滞蔷,何开泽,等.JI J牛膝多糖的体外免疫活忡研究.已投应用环境物学报.
[22]王剑,付田,蒲蔷,何开泽.川牛膝多糖的体内免疫活性研究.张国林中药药理与临床,2007,23(6): 31-33
[23]赵兴梅,徐光忠,李建利,等.川牛膝和怀牛膝的现代药理研究概况.华西药学杂志,2004,19(3):205-207
[24]孙剑,陈朝蔚.阳和汤对兔骨关节炎软骨细胞中结缔组织生长因子表达的影响[J].中国中医骨伤科杂志,2009 ,17(3):56-57
[25]邓博,孙飞,祁开泽,等.复骨键骨片对兔膝关节骨性关节炎软骨细胞凋亡的影响[J].中医正骨,2008 ,9 (9) :15-16
[26]卢思俭,姜全心,王成.益肾为主对兔膝骨性关节炎模型软骨细胞凋亡的影响[J].山东中医药杂志,2006 ,25 (10) :696-698
[27]赵瑜,陈华燕,刘日光,等.补肾康膝方对家兔软骨细胞增殖与凋亡的影响陈述详.时珍国医国药,2008 ,19 (5) :1133-1134
[28]邹丹,全宏勋,胡群员.牛膝精对辐射小鼠造血干细胞增殖与分化的影响.四川中医,2003,21(7):16-17
[29]高晓燕,王大为,李发美,等.牛膝提取物对成骨样细胞增殖的作用.沈阳药科大学学报,2000,17(3):210-213
[30]孙奋勇,潘秋辉,洪岸.牛膝促进成细胞增殖的作用与机理研究. 2004,27(4):264-266
[31]王和鸣,余丹丹,汤亭亭,等.龟鹿二仙胶汤及其拆方对关节软骨细胞增殖的作用[J].中国中医骨伤科杂志, 2007, 15(7 ) :45-47
[32]舒谦,卿茂盛,曹亚飞,等.六味地黄汤含药血清对软骨细胞增殖、凋亡影响的体外实验研究[J].中国中医药科技, 2006, 13(4) : 217
[33]赵湘洪,陈宝兴,丁继华,等.骨碎补对实验性骨性关节炎的治疗作用.中药材,2004,27(4):264-266
[34] Gouze JN,Bordji K,Gulberti S ,et al. lnterleukin-1 beta down-regulates the expression of glucuronosyl transferase1,a key enzyme priming glycosaminoglycan biosynthesis:influence of glucosamine on interleukinl beta mediated effects in rat chondrocytes[J]arthritis Rheum,2001,44(2):351-360
[35] Héraud F, Héraud A , Harmand M F. Apop to sis inno rmal and o steoarth rit ic human art icular cart ilage [J ].A nn Rheum D is, 2000, 59 (12) : 959-965
[36]刘宝新,陈廖斌,汪辉,等.当归阿魏酸钠局部用药治疗骨关节炎的实验研究[J].中国矫形外科杂志,2008 ,16 (17) :1316-1318
[37]王玉彬,陈安民.基质金属蛋白酶家族在骨关节炎软骨组织中表达的研究.中国矫形外科杂志,2007,15(11):36-37
[38] Mehraban F,Lark MV,Ahmed FNetal.[J]. Osteoarthritis Cartilage,1998,6(4):286-294
[39]王毅,邢国胜.IL-1β诱导软骨细胞培养金属蛋白酶/金属蛋白酶抑制剂水平及药物对其影响.中华风湿病学杂志,2003,12(7):718-721
[40]杨坚,史晨辉.MMPs及相关细胞因子在骨性关节炎中的研究. 2009,31(5):448
[41]周晓莉.IL-1在骨关节炎发病及治疗应用中的研究现状.海南医学,2010,21(3):101-103
[42]国延军,牟成林.祛瘀通痹汤治疗原发性膝骨关节炎的临床研究,2009,24(3):21-22
[43]吴剑,鲍同柱.栀子对兔膝骨关节炎模型关节软骨病理改变及IL-1β表达的影响.第二军医大学学报,2009 ,30(3):329-331
[44] Gouze JN,Bordji K,Gulberti S ,et al. lnterleukin-1 beta down-regulates the expression of glucuronosyl transferase1,a key enzyme priming glycosaminoglycan biosynthesis:influence of glucosamine on interleukinl beta mediated effects in rat chondrocytes[J]arthritis Rheum,2001,44(2):351-360
[45] Spencer CM,Wilde MI. Drugs. 1997,53(1):98-106
[1]王玉彬,陈安民.基质金属蛋白酶家族在骨关节炎软骨组织中表达的研究.中国矫形外科杂志,2007,15(17):853-855
[2]刘志翔,张柳.基质金属蛋白酶和骨关节炎的研究进展.华北煤炭医学院学报,2007,9(3) :330-333
[3] Hulejova H , Baresova V , Klezl Z , et al . Increased level of cytokines and mat rix metalloproteinases in osteoart hritic sub2 chondral bone[J].Cytokine,2007,38(3) :151-156
[4] McCachren SS.Expression of metalloproteinases and metalloproteinasenhibitor in human arthritic synovium[J].Arthritis Rheum,1991,34:1085
[5]吕存贤,王维佳.膝骨关节炎病因病理研究及中医治疗概况.浙江中医学院学报,2005,29(1):82-83
[6]梁祖建,韩清民.“补肾活血方”对骨关节炎软骨保护的效应与机制研究.江苏中医药杂志,2009 ,41(3) :33-34
[7]杨坚,史晨辉.MMPs及相关细胞因子在骨性关节炎中的研究.农垦医学, 2009,31:448-451
[8]周晓莉.IL-1在骨关节炎发病及治疗应用中的研究现状.海南医学,2010,21(3):101-103
[9]江锋,陈巍膝.骨性关节炎患者关节滑液肿瘤坏死因子的表达及其临床意义.实用医学杂志,2010,26(2),246-247
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