Objective To investigate the medical effect of the ethanol extract of Acorus gramineus Sol.on arthritis of mice induced by collagen-Ⅱ,and explore the potential pharmacological mechanisms. Methods Arthritis mouse model was established by injection of admixture containing type Ⅱ collagen and Freund's complete adjuvant (FCA) in male BALB/c mice.Mice were divided into five groups:the normal control group (0.9% of sodium chloride solution),the model control group (0.9% of sodium chloride solution),tripterygium group (15 μg·kg-1 of tripterygium tablets), the high-dose of extract of Acorus gramineus Sol. group (60 mg·kg-1 extract of Acorus gramineus Sol.) and the low-dose of extract of Acorus gramineus Sol. group (15 mg·kg-1 extract of Acorus gramineus Sol.).Each group was administered once a day,lasting 21 days.During the experiment,ankles of all mice were measured at predetermined time.At the end of the experiment,blood of the mice was exsanguinated and centrifuged to get serum for measuring the levels of IL-1β,RF and TNF-α.Spleens of mice were dissected and weighed to calculate the spleen index.All arthritis ankles were dissected to make tissue section,and observed under microscope. Results Compared with the model control group,the perimeter of ankle joints of the high-dose of extract of Acorus gramineus Sol. group significantly changed 6 days after administration (P<0.05); That of the low-dose of extract of Acorus gramineus Sol.group significantly changed 12 days after administration (P<0.05); That of tripterygium group significantly changed 9 days after administration (P<0.05).As compared with the normal control group, the spleen index of the model control group was significantly different (P<0.01).As compared with the model control group,the spleen index of tripterygium group,high-dose and low-dose of extract of Acorus gramineus Sol.groups were significantly different (P<0.05).As compared with the normal control group,levels of IL-1β,RF and TNF-α of the model control group were significantly different (all P<0.01).As compared with the model control group,levels of IL-1β,RF and TNF-α of tripterygium group,high-dose and low-dose of extract of Acorus gramineus Sol.groups were significantly decreased. Conclusion Ethanol extracts of Acorus gramineus Sol. have significant therapeutic effect on arthritis mice.The anti-arthritic mechanism is associated with its ability to regulate levels of IL-1β,RF and TNF-α.
Fig.1
Comparison of spleen index among five groups of mice(x̅±s,n=10) Compared with normal control group,*1P<0.01;Compared with model control group,*2P<0.05
Fig.2
Pathological images of the joints in five groups of mice(HE,×200) A.normal control group;B.model control group;C.triptergium group;D.high-dose of ethanol extracts of Acorus gramineus sol.;E.low-dose of ethanol extracts of Acorus gramineus Sol.
表2
Tab.2
表2
表2
5组小鼠血清IL-1β、 RF、TNF-α的水平
Tab.2
Serum levels of IL-1β,RF,and TNF-α in five groups of mice x¯±s,n=10
组别
RF/ (μg·mL-1)
TNF-α
IL-1β
(pg·mL-1)
正常对照组
3.73±0.76
4.02±0.73
16.45±2.87
模型对照组
26.45±5.38*1
24.51±1.07*1
47.76±9.07*1
雷公藤组
15.36±3.09*2
5.46±1.05*3
26.54±5.41*3
金线蒲醇提取物
大剂量组
5.74±1.26*3
4.51±0.87*3
23.64±4.58*3
小剂量组
17.21±3.37*2
5.79±1.14*3
36.81±7.02*2
Compared with normal control group,*1P<0.01;Compared with model control group,*2P<0.05, *3P<0.01
与正常对照组比较,*1P<0.01;与模型对照组比较,*2P<0.05,*3P<0.01
表2
5组小鼠血清IL-1β、 RF、TNF-α的水平
Tab.2
Serum levels of IL-1β,RF,and TNF-α in five groups of mice x¯±s,n=10
BARKSBY HE, LEA SR, PRESHAW PM, et al.The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders[J]. Clin Exp Immunol,2007, 149:217-225.
Understanding cytokine immunobiology is central to the of rational therapies for destructive such as (RA) and . The classical interleukin-1 (IL-1) family cytokines, and , as well as , play key roles in inflammation. Recently, other members of the IL-1 family have been identified. These include six cytokines whose genes are located downstream of the genes for and on 2 (-10) and also , which is the ligand for , a member of the /Toll-like receptor () receptor superfamily. , and Il-1F9 are and, along with their receptor , are highly expressed in epithelial cells suggesting a role in immune defence in the skin and the gastrointestinal (GI) tract including the mouth. Synovial fibroblasts and articular chondrocytes also express and respond to , indicating a possible role in RA. is associated with endothelial cells in the inflamed tissues of patients with RA and , where it is a nuclear factor which regulates . is also an cytokine: it induces the expression of T helper 2 (Th2) cytokines in vitro and in vivo as well as histopathological changes in the lungs and GI tract of . Therapeutic agents which modify IL-1 cytokines (e.g. recombinant IL-1Ra) have been used clinically and others are at various stages of (e.g. anti-antibodies). This review highlights the emerging data on these novel IL-1 cytokines and assesses their possible role in the and therapy of destructive such as RA and .
SEND, GONZALEZ-MAYDAM, BRASINGTON RD.Cardiovascular disease in rheumatoid arthritis[J] . Rheum Dis Clin North Am, 2014,40(1):27-49.
Cardiovascular disease causes significant morbidity and mortality in rheumatoid arthritis (RA). Accelerated atherosclerosis caused by inflammation is the hallmark of cardiovascular disease in RA. Cardiac involvement as an extra-articular manifestation of RA is also prevalent but often subclinical. Treatment of RA also has implications on cardiovascular outcomes in RA. In this article, atherosclerotic and nonatherosclerotic cardiac manifestations in RA are discussed, with a focus on pathogenesis and management.
ZHUL, WEIW, ZHENG YQ, et al.Effects and mechanisms of total glucosides of paeony on joint damage in rat collagen-induced arthritis[J]. Inflamm Res, 2005, 54(5):211-220.
Conclusion: These results indicate that TGP exerts a suppressive effect on joint destruction in rat CIA. The therapeutic effect of TGP could be associated with its ability to ameliorate the secretion and metabolism of synoviocytes and to inhibit the abnormal proliferation and VEGF, bFGF, MMP-1 and MMP-3 production by FLS.
CHEN CX, ZHANGP, PI HF, et al.Extracts of Ariseama Rhizomatum C.E.C. Fischer attenuate inflammatory response on collagen-induced arthritis in BALB/c mice[J]. J Ethnopharmacology, 2011,133:573-582.
LOPATNIKOVA JA, GOLIKOVA EA, SHKARUBA NS, et al.Analysis of the levels of tumour necrosis factor (TNF), autoantibodies to TNF, and soluble TNF receptors in patients with rheumatoid arthritis[J]. Scand J Rheumatol, 2013, 42(6):429-432.
To evaluate the potential contribution made by autoantibodies against tumour necrosis factor (TNF) to the pathogenesis of rheumatoid arthritis (RA). We used affinity chromatography methods and a magnetic separation procedure to purify human autoantibodies specific to TNF. The autoantibodies were used as calibration material to determine the absolute content of autoantibodies to TNF using an enzyme-linked immunosorbent assay (ELISA). TNF content and the levels of soluble TNF receptors types I and II (sTNF-RI and sTNF-RII) were determined using commercial ELISA test kits. We demonstrated significant increases in the levels of TNF, sTNF-RI, and sTNF-RII in the sera of patients with acute RA and in patients with RA who had responded positively to therapy compared with healthy controls. Levels of autoantibodies of the immunoglobulin (Ig)G2, IgG3, and IgG4 subclasses were significantly higher in sera from patients with acute RA than in sera from healthy controls. Level of autoantibodies of the IgG2 subclass were significantly higher in sera from patients with acute RA than in RA patients who had responded positively to therapy. Acute RA is associated with changes in levels of TNF and soluble receptors for TNF and also in levels of autoantibodies to TNF. Given the magnitude of the changes in levels of different subclasses of autoantibodies to TNF, we propose that these autoantibodies might contribute to the pathogenesis of RA.
, 吴永剑
