Longbie capsule combined with bone marrow mesenchymal stem cell transplantation for knee osteoarthritis

doi:10.3969/j.issn.2095-4344.1541

Abstract

Abstract:

BACKGROUND: Previous studies have confirmed that Longbie capsule or bone marrow mesenchymal stem cells alone have a certain therapeutic effect on knee osteoarthritis.
OBJECTIVE: To observe whether Longbie capsule combined with bone marrow mesenchymal stem cell transplantation is better than the single use in the treatment of knee osteoarthritis.
METHODS: Ninety-six adult male Sprague-Dawley rats were randomly divided into four groups: model group, drug group, stem cell group and drug+stem cell group, with 24 rats in each group. Papain was injected into the knee joint cavity of each rat to duplicate the osteoarthritis model. On the 3^rd day after modeling, 0.1 mL of bone marrow mesenchymal stem cell suspension was injected into the knee joint cavity of the rats in the stem cell group, once a week; the water solution of Longbie capsule, 0.937 5 g/kg, was intragastrically injected into the rats in the drug group, twice a week; and the above-mentioned treatments were both performed in the drug+stem cell group. The treatment in each group lasted for 4 weeks. The levels of serum interleukin-1β and interleukin-6 were measured using ELISA before modeling, 3 days after modeling and 4 weeks after administration. Four weeks after administration, the cartilage samples were taken from the right knee joint of each rat for pathological observation with hematoxylin-eosin staining, and for detecting the expressions of collagen type II, Hur, XIAP protein and mRNA using RT-PCR and western blot, respectively.
RESULTS AND CONCLUSION: On the 3^rd day after modeling, the levels of interleukin-1β and interleukin-6 in each group were significantly higher than those before modeling. After 4 weeks of administration, the levels of interleukin-1β in the model group were significantly higher than those in the other three groups (P < 0.05); and the levels of interleukin-1β and interleukin-6 in the drug group and stem cell group were significantly higher than those in the drug+stem cell group (P < 0.05). (2) The surface of articular cartilage tissue in the model group was rough and severely damaged, there were many joint fissures, and the chondrocytes were aggregated and distributed in disorder. The damaged cartilage tissues were partially repaired in the drug group and stem cell group, with the smoother surface of cartilage tissue and fewer joint fissures than the model group, and there were also increased and evenly distributed chondrocytes in the former two groups. The surface of articular cartilage in the drug+stem cell group was smooth, and the chondrocytes were regular and uniformly arranged without joint fissures. (3) The expression of type II collagen, Hur, XIAP protein (or gene) in the model group was lower than that in the other three groups (P < 0.05), and the expression of type II collagen, Hur, and XIAP protein (or gene) in the drug group and stem cell group was lower than that in the drug+stem cell group (P < 0.05). These results indicate that Longbie capsule combined with bone marrow mesenchymal stem cell transplantation is superior to Longbie capsule or bone marrow mesenchymal stem cell transplantation used alone in the treatment of knee osteoarthritis.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Osteoarthritis, Knee, Bone Marrow, Mesenchymal Stem Cells, Interleukin-1beta, Interleukin-6, Collagen Type II, Tissue Engineering

CLC Number:

Chen Peng, Shi Xiaotian, Guo Yu, Qiu Xunyong, Wang Yan. Longbie capsule combined with bone marrow mesenchymal stem cell transplantation for knee osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(5): 797-802.

Figures/Tables 5

References

[1] 张中原,余丽梅,王信. 膝骨关节炎再生修复治疗新方法研究进展[J].实用医学杂志, 2018,34(9):1561-1564.

[2] Glyn-Jones S, Palmer AJ, Agricola R, et al. Osteoarthritis. Lancet. 2015;386(9991):376-387.

[3] 张钟元,江和训,赵锦伟,等.关节镜清理联合自体骨髓间充质干细胞移植治疗膝骨关节炎疗效观察[J].风湿病与关节炎, 2018,7(6):39-42.

[4] 张春琪.自体骨髓间充质干细胞治疗早期膝骨性关节炎的临床研究[D].郑州:河南中医药大学,2015.

[5] 孟庆阳,张玉可,孟繁琪. 锁定钢板植骨内固定配合中药治疗胫骨中下段骨折不愈合[J].河南科技大学学报(医学版), 2018,36(1):37-39.

[6] 王在凤. 补肾活血中药治疗骨质增生继发性腰痛的效果及对患者骨硬化素蛋白水平的影响[J].中国当代医药,2018,25(8):158-160.

[7] 干群.补肾活血中药治疗骨质增生继发性腰痛疗效及对DKK1、SOST水平的影响[J].全科医学临床与教育, 2017,15(4):404-408.

[8] 潘建科,郭柏铭,刘军,等. 龙鳖胶囊对骨髓间充质干细胞增殖活性的影响[J].中国组织工程研究,2015,19(28):4439-4444.

[9] 杨帆,袁芳,侯秀娟,等.补肾通络方对大鼠膝骨关节炎膝关节软骨细胞外基质代谢的影响[J].吉林中医药,2018,38(1):67-71.

[10] Chen X, Yan J, He F, et al. Mechanical stretch induces antioxidant responses and osteogenic differentiation in human mesenchymal stem cells through activation of the AMPK-SIRT1 signaling pathway.Free Radic Biol Med. 2018;126:187-201.

[11] Han GE, Kang HT, Chung S, et al. Novel neohesperidin dihydrochalcone analogue inhibits adipogenic differentiation of human adipose-derived stem cells through the nrf2 pathway. Int J Mol Sci. 2018;19(8): E2215.

[12] 李永津,林涌鹏,侯宇,等.龙鳖胶囊与骨髓间充质干细胞移植对膝骨关节炎大鼠软骨修复作用的比较研究[J].广州中医药大学学报, 2018,35(1): 123-128.

[13] 安玉芳,李义,崔立建,等.乌头注射液关节腔注射对膝骨关节炎模型兔关节液IL-1β、IL-18、NF-κB p65的影响[J].中国中医药科技, 2017,24(6): 736-738.

[14] 袁颖超,廖秋菊. 炎性细胞因子与膝骨关节炎诊断及治疗的最新研究进展[J].药学实践杂志,2018,36(1):9-12.

[15] 任海亮,马剑雄,马信龙. 膝骨关节炎时关节滑液中炎症相关物质的表达[J].中国组织工程研究,2015,19(15):2336-2340.

[16] 郑卫军,宋祖权,孙红桥. 血清IL-1β和IL-6表达水平与膝骨关节炎病程关系的研究[J].临床外科杂志,2011,19(7):490-492.

[17] 窦浚峰,海国栋,封青川,等.尼古丁对白细胞介素-1β诱导的软骨细胞炎性反应及核因子-κB信号通路的影响[J].中华实验外科杂志, 2018,35(5): 885-887.

[18] 程晓平,林炜,陈兆榕. 独活寄生汤含药血清抑制IL-1β诱导的软骨细胞炎症反应的机制研究[J].风湿病与关节炎,2017,6(4):5-8.

[19] 李菁,赵岩. 白细胞介素6及其受体拮抗剂在类风湿关节炎发病机制及治疗中的作用[J].中华医学杂志,2014,94(39):3114-3116.

[20] 潘建科,罗斌,郭达,等.龙鳖胶囊对膝骨关节炎大鼠IL-1β、IL-6、IL-10水平的影响[J].中华中医药杂志,2015,30(5):1675-1679.

[21] 刘康妍,凌龙,胡海澜. 骨关节炎的退变进程及其诊断分期[J].中华关节外科杂志(电子版),2017,11(4):442-445.

[22] 王舒婷,陈志煌,侯春福,等.经筋微创松解疗法对膝骨关节炎兔软骨细胞凋亡的抑制作用及机制[J].山东医药,2017,57(21):30-32.

[23] Sun J, Wei X, Wang Z, et al. Inflammatory milieu cultivated Sema3A signaling promotes chondrocyte apoptosis in knee osteoarthritis.J Cell Biochem. 2018;119(3):2891-2899.

[24] Jiang X, Yin L, Zhang N, et al. Bisphenol A induced male germ cell apoptosis via IFNβ-XAF1-XIAP pathway in adult mice. Toxicol Appl Pharmacol. 2018;355:247-256.

[25] 周俊,单慧蓉,王小龙,等.CDK4/6对急性白血病细胞增殖及凋亡的影响[J].江苏医药,2017,43(17):1209-1212.

[26] Zhang X, Zou T, Rao JN, et al. Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines.Nucleic Acids Res. 2009;37(22):7623-7637.

[27] Alcaraz MJ, Megías J, García-Arnandis I, et al. New molecular targets for the treatment of osteoarthritis. Biochem Pharmacol. 2010;80(1):13-21.

[28] 贾博,林福庆. 膝骨关节炎关节镜下病变特征与血清CTX-Ⅱ和COMP水平的相关性[J].临床骨科杂志,2018,21(2):185-189.