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Experimental And Clinical Studies Of Langchuangjing Granule On The Expression Of Intercelluar Adhesion Molecule-1 In Mice And Patients With Active SLE

Posted on:2004-03-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:W DingFull Text:PDF
GTID:1104360095955675Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Systemic lupus erythematosus(SLE) is an autoimmune disease with specificity caused by various factors. Its incidence rate is 70.4 in 100 thousand in our country.and that of women from report attains 115 in 100 thousand.The disease,with chronic clinical duration, whose recurrence and remission exchange, affects every organ system.Renal failure, infection and damage of central nervous system are its underlying cause of death.which seriously threaten patients' health and life. SLE is one of the difficult problems in medical field. 'Langchuangjing Granule'(LG) is an effective preparation from pure Chinese herbs in treating SLE. On the basis of former research,this paper proceeded research from experiment and clinic.regarded intercellular adhesion molecule(ICAM-1 or CD54) as cardinal observe object.and tried to expatiate on its approach,tache and target.The experimental research consisted of two parts: pharmacology and toxicology studies. In pharmacology research, inborn NZB/W F1(NZB/NZW F1 or BW) lupus-prone mice were choosed to examine the expression of ICAM-1 in serum, peripheral blood lymphocyte and monocyte and kidney respectively.The results showed that in female NZB/W F1 mice of 3 month, the serum level of soluable intercellular adhesion molecule-1(slCAM-1) was in the normal range.without proteinuria and obvious histopathological changes of kidneys.but high expression of ICAM-1 in peripheral blood lymphocyte and monocyte and kidney was detected already;to the 7 month, the serum level of sICAM went up obviously in female NZB/W F1 mice with abnormality of uria protein and kidney function. LG can effectively restrain high expression of ICAM-1 in peripheral blood lymphocyte and monocyte surface and renal tissue, and elevation of glomerulus cell number and serum slCAM-1 in female NZB/WF1 mice. It also can lower the level of proteinuria, improve renal function and increase immuno-organ index.When combined with western medicines, LG showed synergism,which revealed the obvious advantage of integration of Chinese herbs and western medicines.In toxicology research, median lethal dose(LD50) and maximum tolerance dose of LG(ig) were observed. LD50 of LG couldn't be completed because of its preparation,its maximum tolerance dose was 304g gruffs-kg-1-d-1,equal to 87 times of its clinical dosage, which indicated that LG was safe without poison.In clinical research, 46 involved active SLE patients were randomly divided into western medicine group(20 cases.WM as a control) and LG+WM group(26 cases,treated by LG integrating with western medicines),and were treated six months.The effects of LG on clinical efficacy and SLAM disease active scales were observed.Glucocorticoid index(GC index) and CTX index were introduced to analyze the effect of LG on reduce dosage of western medicine.At the same time, the levels of serum sICAM-1, before and after treatment, were investigated.As a result, the levels of serum slCAM-1 in LG+WM and WM groups, after treatment.decreased more remarkably compared with that before treatment(P<0.001,0.01).LG+WM group was much better than WM group in the aspects of clinical curative effect, lowering the disease active scales and reduceing dosage of GC and immunosuppressive agent etc.The results above showed that LG could effectively restrain elevation of ICAM-1, develop the synergy and increase curative effect when integrating with western medicines.which followed the optimization principle of system theory virtually. We postulate that LG possess an effect like GC or anti-cell adhesion molecule, its curative effect mechanism was associated with preventing ICAM-1 and cytokines such as slL-2R,TNF-a etc from going up.and suppressing excessive activation of T and B cells, and inflammatory cell infiltration, improving disfunction of T and B cells, reducing excessive formation of the autoantibody and immunecomplex.Its accurate mechanism needs further research.This paper observed the effect of the preparation from pure Chinese herbs on ICAM-1 in inborn NZB/W F1 lupus-prone mice by flow cy...
Keywords/Search Tags:Systemic lupus erythematosus, Langchuangjing Granule, Cell adhesion molecule, Intercellular adhesion molecule-1, Experimental research, Animal model, NZB/W F1 mice, Flow cytometric analysis, Immunohistochemistry, T lymphocyte, Monocyte, Clinical research
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