Effect of combined methotrexate and cyclophosphamide therapy on the expression of B cell activation factor belonging to the TNF family in the salivary glands of mice with induced Sj(o)gren's syndrome
10.3760/cma.j.issn.1007-7480.2009.09.006
- VernacularTitle:周期联合甲氨蝶呤和环磷酰胺治疗诱导型干燥综合征小鼠及对涎腺B淋巴细胞刺激因子表达影响的研究
- Author:
Ke XU
;
Wenpeng ZHAO
;
Yuehong HUO
;
Hua WEI
;
Fang LI
;
Lin ZHANG
;
Fengchun ZHANG
;
Xiaofeng LI
- Publication Type:Journal Article
- Keywords:
Sjogren's syndrome;
Salivary glands;
Methotrexate;
Cyclophosphamide
- From:
Chinese Journal of Rheumatology
2009;13(9):603-607
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of combination therapy by observing the salivary glands function and related organ pathology after given methotrexate (MTX) and cyclophosphamide (CTX) intermittently in induced mice model of Sjogren's syndrome (SS). To further explore the synergistic effect of combination therapy by detecting the immunological regulatory factor B cell activation factor belonging to the TNF family (BAFF) expression. Methods The ingredients of Lewis rat's exocrine glands homogenate were injected into female C57BL/6 mice to set up the mice model of SS. After established the SS mice model successfully, they were randomly divided into six SS model group, including low-dose MTX treatment group (0.02 mg/w), high-dose MTX treatment group (0.06 mg/w), CTX pause treatment group (1.2 mg/3 w), CTX alternate day treatment group (0.6 mg/2 d), MTX+CTX combination treatment group (MTX 0.02 mg/3 w+ CTX 1.2 mg/3 w). Treatment effects were assessed both clinically and histologically. Results Eighteen weeks after the first treatment, the improvement of the salivary secretion of the CTX alternate day treatment group and MTX+CTX combination treatment group were higher than other groups, which showed statistically significant difference (P<0.01). Compared with the SS model control group, HE staining showed that the lymphocytic infiltration of exoerine glands was decreased in the treatment group. In the CTX alternate day treatment group and MTX+CTX combination treatment group, few amount of inflammatory cell infiltration were found, and the expression intensity of BAFF mRNA and protein were decreased markedly in salivary gland than others by RT-PCR and immunohistochemistry assay (P<0.01). Conclusion MTX and CTX can inhibit lymphocytic infiltration of the salivary glands, inhibit BAFF transcriptional level and production of BAFF protein, leading to an increase of fluid production. It suggests that modulation of signaling via BAFF pathways may be a mechanism of action. MTX and CTX combination therapy is more effective than single-agent therapy. The inhibitory effects of MTX and CTX on BAFF-mediated inflammatory pathways are primarily synergistic.
