The Study Of The Therapeutic Effect Of Pentapeptide Compound CMS010.26 On Asthma And Systemic Lupus Erythematosus(SLE) And Its Therapeutic Mechanisms

Objective:To research the effects of Pentapeptide compound CMS010.26 on the unspecific proliferation of T lymphocytes and effects on the T lymphocyte subset differentiation. To research the therapeutic effects of CMSTO 10.26 on the allergic asthma (AA) and systemic lupus erythematosus (SLE) and its possible mechanisms.Methods:1. The inhibiting effect of CMS010.26 (100-0.01μg/ml) in vitro on T lymphocytes proliferation was assayed by MTT method.2. The inhibiting effect of CMS010.26 (200μg/kg/d, 100μg/kg/d, and 50μg/kg/d) in vivo on T lymphocytes proliferation was assayed by MTT method.3. The immune effect of CMS010.26 (200μg/kg/d, 100μg/kg/d, and 50μg/kg/d) on rats T lymphocytes differentiation was detected by flow cytometry.4. Wistar rats were divided into five groups: CMS010.26 (200μg/kg/d, 100μg/kg/d), dexamethasone, saline control and normal control. Twice injections of OVA antigen Fluid in multi-subcutaneous per Wistar rat was used to induce AA. From 15^th days of the first injection, rats were given ultrasonic atomizing inhalation of OVA once per day and it last 7 days. From 1^st days of the first injection, they were given drugs. Attack of AA, respiration curve, serologic alteration and HE and PAS stain were used to observe the therapeutical effect of CMS010.26 on pathological damage of lungs.5. Wistar rats were divided into five groups in the same way as above. The immune effect of CMS010.26 on asthma rats CD4⁺ and CD8⁺T lymphocytes differentiation in blood and bronchoalveolar lavage fluid (BALF) was detected by flow cytometry. At the same time detected the effect of CMS010.26 on asthma rats Th1, Th2 lymphocyte subsets in blood.6. (DBA/2xC57BL/J6) Fl hybrid mice were divided into four groups: CMS010.26 (200ng/kg/d, lOOug/kg/d), saline control and normal control. Four injections of lymphocytes of parental generation were given to the Fl hybrid mice every three days to induce SLE. From 15th days of the first injection, mice were given drugs. Urine protein, renal index, serologic alteration and HE, PAS and Masson stain were detected to observe the therapeutical effect of CMSO 10.26 on the pathological damage of kidney.7. Fl hybrid mice were divided into four groups in the same way as above. The immune effect of CMS010.26 on SLE mice CD4+ and CD8+T lymphocytes differentiation in blood was detected by flow cytometry.Results:1. CMS010.26 (0.01-lOOug/ml) in vitro can inhibit ConA induced T lymphocytes proliferation (P<0.05).2. CMS010.26 (200ug/kg/d, lOOug/kg/d) in vivo (i.p.) can significantly inhibit ConA induced T lymphocytes proliferation (P<0.05).3. CMSO 10.26 (200ug/kg/d, lOOug/kg/d, 50ug/kg/d) can decrease rats CD4+/CD8+ (P<0.05).4. CMS010.26 (200ug/kg/d, lOOug/kg/d) can relieve the attack of AA, inhibit the inflammatory cell infiltration including eosinophils (EOS) and neutrophils (P<0.05), and inhibit the proliferation of goblet cells.5. CMS010.26 (200ug/kg/d, 1 OOug/kg/d) can decrease CD4+/CD8+ in AA rats' blood. Meanwhile it can decrease it's percentage of Thl and Th2 lymphocytes. CMS010.26 can increase the percentage of CD4+ T lymphocytes in BALF and at the same time decrease its percentage of CD8+ T lymphocytes, thus increase its CD4+/CD8. All of the above results showed statistic significant difference (.P<0.05).6. CMSO 10.26 (200ug/kg/d, 100|ig/kg/d) can decrease the urine protein, Serum creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC) and total triglyceride (TG). It can also decrease anti-dsDNA antibody and anti-histone antibody. All of the above results showed statistic significant difference (P<0.05). HE, PAS and Masson stain indicated that the pathological changes in kidney were relieved to some extent.7. CMSO 10.26 (200ug/kg/d, lOOug/kg/d) can decrease the percentage of CD4+ T lymphocytes, CD8+ T lymphocytes, and CD4+/CD8+ in SLE mice's blood (P<0.05). Conclusions:1. CMSO 10.26 has therapeutic effect on AA. It may produce its therapeutic effect by inhibiting T lymphocytes proliferation, decreasing CD4+/CD8+ in blood redressing CD4+ and CD8+ T lymphocytes disequilibrium in blood and BALF.2. CMSO 10.26 has therapeutic effect on SLE. It may produce its therapeutic effect by decreasing CD4+/CD8+ in blood redressing CD4+ and CD8+ T lymphocytes disequilibrium in blood.