[1]邢润麟,王培民,张农山,等.中医“肝肾同源”理论异病同治膝骨关节炎和绝经后骨质疏松症的实验理论基础研究[J].中医正骨,2017,29(01):1-10.
　XING Runlin,WANG Peimi,ZHANG Nongshan,et al.Application of TCM theory of HOMOGENY OF LIVER AND KIDNEY and TREATING DIFFERENT DISEASES WITH SAME METHOD to treatment of knee osteoarthritis and postmenopausal osteoporosis:an experimental research of theoretical foundation[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2017,29(01):1-10.
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中医“肝肾同源”理论异病同治膝骨关节炎和绝经后骨质疏松症的实验理论基础研究()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第29卷
期数:
2017年01期
页码:
1-10
栏目:
基础研究
出版日期:
2017-01-20

文章信息/Info

Title:
Application of TCM theory of HOMOGENY OF LIVER AND KIDNEY and TREATING DIFFERENT DISEASES WITH SAME METHOD to treatment of knee osteoarthritis and postmenopausal osteoporosis:an experimental research of theoretical foundation
作者:
邢润麟; 王培民; 张农山; 李晓辰; 赵凌睿; 张立
南京中医药大学附属医院,江苏 南京 210029
Author(s):
XING Runlin; WANG Peimi; ZHANG Nongshan; LI Xiaochen; ZHAO Lingrui; ZHANG Li
The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine,Nanjing 210029,Jiangsu,China
关键词:
骨关节炎; 膝;  骨质疏松; 绝经后;  肝肾同源;  异病同治;  动物实验;  大鼠; Sprague-Dawley
Keywords:
osteoarthritis; knee;  osteoporosis; postmenopausal;  homogeny of liver and kidney;  treating different diseases with same method;  animal experimentation;  rats; Sprague-Dawley
摘要:
目的:从骨代谢角度探讨依据中医“肝肾同源”理论异病同治膝骨关节炎(knee osteoarthritis,KOA)和绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)的实验理论基础。方法:将60只8月龄SPF级雌性SD大鼠随机分为空白组、KOA组和PMOP组。空白组大鼠不进行任何处理,KOA组和PMOP组分别采用改良Hulth法和去卵巢法制作KOA和PMOP大鼠模型。分别于造模后7、28、56 d从各组随机选取6只大鼠测定股骨骨密度,抽取腹主动脉血测定血清中抗酒石酸酸性磷酸酶5b(tartrate resistant acid phosphatase-5b,TRACP-5b)、骨碱性磷酸酶(bone alkaline phosphatase,BALP)、Ⅰ型前胶原氨基端前肽(N-terminal propeptide of typeⅠprecollagen,PⅠNP)、Ⅰ型前胶原羧基端前肽(C-terminal propeptide of typeⅠprecollagen,PⅠCP)、Ⅰ型胶原羧基端交联端肽(C-terminal cross-linked telopeptides of typeⅠcollagen,CTX-Ⅰ)、Ⅰ型胶原氨基端交联端肽(N-terminal cross-linked telopeptides of typeⅠcollagen,NTX-Ⅰ)、白细胞介素-1β(interleukin-1β,IL-1β)、IL-6、IL-8、IL-10、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)及MMP-13含量,切取双侧后肢膝关节软骨组织制成切片,在光镜下观察其形态,并采用Mankin's评分标准进行评分。结果:造模后7、28、56 d时各组大鼠股骨骨密度和血清中TRACP-5b、BALP、PⅠNP、PⅠCP、CTX-Ⅰ、NTX-Ⅰ、IL-1β、IL-6、IL-8、IL-10、TNF-α、MMP-9、MMP-13含量及膝关节软骨Mankin's评分总体比较,组间差异均有统计学意义。造模后7 d时,KOA组与空白组骨密度比较,差异无统计学意义(P=0.059),PMOP组骨密度低于空白组(P=0.005); 造模后28、56 d时,KOA组和PMOP组骨密度均低于空白组(P=0.000,P=0.002; P=0.003,P=0.000)。造模后各时点KOA组和PMOP组血清TRACP-5b浓度均高于空白组(P=0.015,P=0.013,P=0.000; P=0.000,P=0.000,P=0.000),BALP浓度均高于空白组(P=0.000,P=0.003,P=0.001; P=0.000,P=0.000,P=0.000),PⅠNP浓度均低于空白组(P=0.000,P=0.003,P=0.000; P=0.000,P=0.000,P=0.000),PⅠCP浓度均低于空白组(P=0.005,P=0.000,P=0.001; P=0.000,P=0.005,P=0.000),CTX-Ⅰ浓度均高于空白组(P=0.000,P=0.002,P=0.003; P=0.000,P=0.000,P=0.000),NTX-Ⅰ浓度均高于空白组(P=0.000,P=0.000,P=0.008; P=0.005,P=0.003,P=0.000),IL-1β浓度均高于空白组(P=0.023,P=0.003,P=0.006; P=0.013,P=0.006,P=0.003),IL-8浓度均高于空白组(P=0.000,P=0.000,P=0.000; P=0.008,P=0.000,P=0.000),IL-10浓度均低于空白组(P=0.032,P=0.029,P=0.013; P=0.010,P=0.000,P=0.000),TNF-α浓度均高于空白组(P=0.000,P=0.000,P=0.009; P=0.000,P=0.016,P=0.006); 造模后各时点KOA组血清IL-6浓度均高于空白组(P=0.026,P=0.003,P=0.000),造模后28、56 d时PMOP组血清IL-6浓度均高于空白组(P=0.023,P=0.006),造模后7 d时PMOP组血清IL-6浓度与空白组比较,差异无统计学意义(P=0.068)。造模后各时点KOA组和PMOP组血清MMP-9浓度均高于空白组(P=0.000,P=0.021,P=0.002; P=0.002,P=0.018,P=0.000),MMP-13浓度均高于空白组(P=0.000,P=0.000,P=0.000; P=0.000,P=0.010,P=0.000)。造模后各时点KOA组关节软骨Mankin's评分均高于空白组(P=0.000,P=0.000,P=0.000); 造模后7、28 d时,PMOP组Mankin's评分与空白组比较,差异均无统计学意义(P=0.082,P=0.056),造模后56 d时PMOP组Mankin's评分高于空白组(P=0.043)。结论:KOA从早期开始即存在与PMOP类似的高转换型骨代谢紊乱,而PMOP中后期也会出现类似KOA的软骨退变; 高转换型骨代谢紊乱可能在KOA和PMOP的发病中具有同样重要的作用,这可作为中医学根据“肝肾同源”理论对KOA和PMOP进行异病同治的实验理论基础。
Abstract:
Objective:To explore the experimental theoretical foundation for treating knee osteoarthritis(KOA)and postmenopausal osteoporosis(PMOP)with same method under the guidance of TCM theory of HOMOGENY OF LIVER AND KIDNEY through bone metabolism experimentation.Methods:Sixty 8-month-old SPF-grade female SD rats were randomly divided into blank group,KOA group and PMOP group.The rats in blank group did not receive any treatment,while the KOA rat models were built by using improved Hulth method in KOA group and the PMOP rat models were built by ovariectomy in PMOP group.Six rats were randomly selected from each group at 7,28 and 56 days after the modeling respectively and their femoral bone mineral densities(BMD)were measured.Their blood was drawn from abdominal aorta and the serum contents of tartrate resistant acid phosphatase-5b(TRACP-5b),bone alkaline phosphatase(BALP),N-terminal propeptide of typeⅠprecollagen(PⅠNP),C-terminal propeptide of typeⅠprecollagen(PⅠCP),C-terminal cross-linked telopeptides of typeⅠcollagen(CTX-Ⅰ),N-terminal cross-linked telopeptides of typeⅠcollagen(NTX-Ⅰ),interleukin-1β(IL-1β),IL-6,IL-8,IL-10,tumor necrosis factor-α(TNF-α),matrix metalloproteinase-9(MMP-9)and MMP-13 were measured.The knee articular cartilage tissues of bilateral posterior limbs were sectioned for HE staining and their morphous were observed under light microscope and were evaluated by using Mankin's scoring standard.Results:There was statistical difference in femoral BMD and serum contents of TRACP-5b,BALP,PⅠNP,PⅠCP,CTX-Ⅰ,NTX-Ⅰ,IL-1β,IL-6,IL-8,IL-10,TNF-α,MMP-9,MMP-13 and Mankin's scores of knee articular cartilage between the 3 groups at 7,28 and 56 days after the modeling respectively.There was no statistical difference in femoral BMD between KOA group and blank group(P=0.059)and the femoral BMD were lower in PMOP group compared to blank group(P=0.005)at 7 day after the modeling.The femoral BMD were lower in KOA group and PMOP group compared to blank group at 28 and 56 days after the modeling(P=0.000,P=0.002; P=0.003,P=0.000).At each time point after the modeling,the serum concentration of TRACP-5b were higher in KOA group and PMOP group compared to blank group(P=0.015,P=0.013,P=0.000; P=0.000,P=0.000,P=0.000),the serum concentration of BALP were higher in KOA group and PMOP group compared to blank group(P=0.000,P=0.003,P=0.001; P=0.000,P=0.000,P=0.000),the serum concentration of PⅠNP were lower in KOA group and PMOP group compared to blank group(P=0.000,P=0.003,P=0.000; P=0.000,P=0.000,P=0.000),the serum concentration of PⅠCP were lower in KOA group and PMOP group compared to blank group(P=0.005,P=0.000,P=0.001; P=0.000,P=0.005,P=0.000),the serum concentration of CTX-Ⅰwere higher in KOA group and PMOP group compared to blank group(P=0.000,P=0.002,P=0.003; P=0.000,P=0.000,P=0.000),the serum concentration of NTX-Ⅰwere higher in KOA group and PMOP group compared to blank group(P=0.000,P=0.000,P=0.008; P=0.005,P=0.003,P=0.000),the serum concentration of IL-1β were higher in KOA group and PMOP group compared to blank group(P=0.023,P=0.003,P=0.006; P=0.013,P=0.006,P=0.003),the serum concentration of IL-8 were higher in KOA group and PMOP group compared to blank group(P=0.000,P=0.000,P=0.000; P=0.008,P=0.000,P=0.000),the serum concentration of IL-10 were lower in KOA group and PMOP group compared to blank group(P=0.032,P=0.029,P=0.013; P=0.010,P=0.000,P=0.000),the serum concentration of TNF-α were higher in KOA group and PMOP group compared to blank group(P=0.000,P=0.000,P=0.009; P=0.000,P=0.016,P=0.006).The serum concentration of IL-6 were higher in KOA group compared to blank group at each time point after the modeling(P=0.026,P=0.003,P=0.000).The serum concentration of IL-6 were higher in PMOP group compared to blank group at 28 and 56 days after the modeling(P=0.023,P=0.006).There was no statistical difference in serum concentration of IL-6 between PMOP group and blank group at 7 day after the modeling(P=0.068).At each time point after the modeling,the serum concentration of MMP-9 were higher in KOA group and PMOP group compared to blank group(P=0.000,P=0.021,P=0.002; P=0.002,P=0.018,P=0.000),the serum concentration of MMP-13 were higher in KOA group and PMOP group compared to blank group(P=0.000,P=0.000,P=0.000; P=0.000,P=0.010,P=0.000).The Mankin's scores of knee articular cartilage were higher in KOA group compared to blank group at each time point after the modeling(P=0.000,P=0.000,P=0.000).There was no statistical difference in Mankin's scores of knee articular cartilage between PMOP group and blank group at 7 and 28 days after the modeling(P=0.082,P=0.056).The Mankin's scores of knee articular cartilage were higher in PMOP group compared to blank group at 56 days after the modeling(P=0.043).Conclusion:The high-turnover-type bone metabolic disorder can be found in KOA from the early period and the cartilage degeneration can be found in PMOP in the middle and later period,so PMOP is similar to KOA in these features.The high-turnover-type bone metabolic disorder may play an equally important role in morbidity of KOA and PMOP,so it can be considered as the experimental theoretical foundation for treating KOA and PMOP with same method according to the TCM theory of HOMOGENY OF LIVER AND KIDNEY.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金项目(81573993); 江苏省自然科学基金项目(BK20151598); 南京中医药大学附属医院院级课题(Y14022)
通讯作者:王培民 E-mail:drwpm@163.com
更新日期/Last Update: 2017-01-20