Difference between CIA Rat Models of Different Ages and Intervention Effect and Safety of Modified Shaoganfuzi Decoction

doi:10.19803/j.1672-8629.2021.12.06

Abstract

Abstract: Objective To investigate the difference between collagen-induced arthritis (CIA) models of rats of different ages, and to study the effect of modified Shaoganfuzi decoction on the expression of inflammatory cytokines and its safety.Methods Forty young rats and forty old rats were randomly divided into four groups: the normal group, model group, control group and TCM group. Except the normal group, CIA models were established in all the other groups, and intragastric intervention was performed for 4 weeks after modeling. The conditions of the rats were observed, the drainage volume of the ankle was measured, the inflammation index (AI) was evaluated, the organ index after the last administration was calculated, and cytokines and safety indicators were detected. Results In the third week of modeling, the drainage volume of right feet in the elder model group was higher than that in the young model group (P<0.05). Two to four weeks into modeling, the AI scores of the elder model group were higher than those in the young group (P<0.05). The thymus indexes of the normal group, model group and control group were lower than those of the young group (P<0.01). Levels of γ-interferon(INF-γ), interleukin-2(IL-2), interleukin-6(IL-6), interleukin 17A(IL-17A) and tumor necrosis factor-α(TNF-α) in the elder TCM group were lower than in the model group (P<0.05). The level of IL-17A in the elder TCM group was lower than in the control group (P<0.05). The levels of TNF-α, IL-6, IL-17A and creatinine (CREA) in the young TCM group were lower than in the model group and the control group (P<0.05). Levels of alanine aminotransferase (ALT) in the elder and young TCM groups were lower than in the control group (P<0.05). Levels of creatine kinase isoenzyme (CK-MB) and troponin I (cTnI) in both the elder and young TCM groups were lower than in the model group and control group (P<0.05).Conclusion There are differences in the severity of joint inflammation between CIA rats of different ages. The modified Shaoganfuzi decoction is safe and effective. Thymus degeneration caused by ageing may account for the difference between EORA and YORA.

Key words: collagen-induced arthritis, modified Shaoganfuzi decoction, inflammatory cytokines, safety indicators, thymus degeneration

CLC Number:

R971.1

ZHANG Yuting, ZHU Yuelan, HOU Xiujuan. Difference between CIA Rat Models of Different Ages and Intervention Effect and Safety of Modified Shaoganfuzi Decoction[J]. Chinese Journal of Pharmacovigilance, 2021, 18(12): 1129-1133.

References

[1] Lahaye C, Tatar Z, Dubost JJ, et al.Overview of biologic treatments in the elderly[J]. Joint Bone Spine, 2015, 82(3): 154-160.
[2] Li ZG, Wang H.Progress in diagnosis and treatment of elderly onset rheumatoid arthritis[J]. Practical Geriatrics(实用老年医学), 2008, 22(1): 7-11.
[3] Kim EJ, Lee J, Ryu YS, et al.Shared epitope and radiologic progression are less prominent in elderly onset RA than young onset RA[J]. Rheumatol Int, 2013, 33(8): 2135-2140.
[4] Zhang JF, Ye XL, Duan M, et al.Clinical characteristics of elderly and younger onset rheumatoid arthritis[J]. National Medical Journal of China(中华医学杂志), 2020, 100(47): 3788-3792.
[5] Wang ST, Liu J, Wei S.Comparative study of elderly-onset versus young-onset rheumatoid arthritis: clinical features and treatment[J]. Chinese Journal of Geriatrics(中华老年医学杂志), 2017, 36(6): 665-668.
[6] Dejaco C, Duftner C, Wipfler-Freissmuth E, et al.Elderly versus younger onest rheumatoid arthritis:higher levels of ultrasound-detected inflammation despite comparable clinical disease activity[J]. Arthritis Care Res(Hoboken), 2013, 65(2): 304-308.
[7] Vasco C, Romã O, Frances H, et al.Treatment-resistant synovitis and radiographic progression are increased in elderly-onset rheumatoid arthritis patients: findings from a prospective observational longitudinal early arthritis cohort study[J]. Seminars in Arthritis and Rheumatism, 2020, 50(4): 735-743.
[8] Van Onna M, Boonen A.The challenging interplay between rheumatoid arthritis, ageing and comorbidities[J]. BMC Musculoskelet Disord, 2016, 17: 184.
[9] Xu W, Wong G, Hwang YY, et al.The untwining of immunosenes-cence and aging[J]. Semin Immunopathol, 2020, 42(5): 559-572.
[10] Dai XN, Liu J.Research progress in elderly-onset rheumatoid arthritis[J]. Chinese Journal of Practical Internal Medicine(中国实用内科杂志), 2019, 39(6): 562-567.
[11] Ye J, Huang X, Hsueh EC, et al.Human regulatory T cells induce T-lymphocyte senescence[J]. Blood, 2012, 120(10): 2021-2031.
[12] Liu X, Mo W, Ye J, et al.Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition[J]. Nat Commun, 2018, 9(1): 249.
[13] Jeffrey BH.Hazzard’s Geriatric Medicine And Gerontology (6th edition)(哈兹德老年医学(第6版)) [M]//Li XY, Wang JY. Beijing: People’s Military Medical Publishing House, 2015.
[14] Boots AM, Maier AB, Stinissen P, et al.The influence of ageing on the developm-ent and management of rheumatoid arthritis[J]. Nat Rev Rheumatol, 2013, 9(10): 604-613.
[15] Weyand CM, Goronzy JJ.Aging of the immune system. mechanisms and therapeutic targets[J]. Ann Am Thorac Soc, 2016, 13(Suppl 5): S422-S428.
[16] Zhou QL, Yang XW.Four new ginsenosides from red ginseng with inhibitory activity on melanogenesis in melanoma cells[J]. Bioorg Med Chem Letter, 2015, 2(16): 3112-3116.
[17] Bao CL, Qiao LG, Yan YW, et al.Increased serum interleukin-2 levels are associated with abnormal peripheral blood natural killer cell levels in patients with active rheumatoid arthritis[J]. Mediators of Inflammation, 2020: 6108342.
[18] Weyand CM, Yang Z, Goronzy JJ.T-cell aging in rheumatoid arthritis[J]. Curr Opin Rheumatol, 2014, 26(1): 93-100.
[19] Bauer ME.Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression[J]. Immun Ageing, 2020, 17: 6.
[20] Zheng W, Zhu YL, Ma JF, et al.Clinical observation on Jiawei Shaogan Fuzi decoction combined with western medicine in the treatment of 30 rheumatoid arthritis patients with cold-damp obstruction syndrome at active phase[J]. Journal of Traditional Chinese Medicine(中医杂志), 2018, 59(9): 760-764.
[21] Jing WX, Hou XJ, Sun WY, et al.Adding Shaogan Fuzi Tang to influence of relative gene expression of the JAK/STAT signaling pathway of the joint synovial tissue in CIA rat[J]. Acta Chinese Medicine(中医学报), 2016, 31(4): 545-549.