Leung M K, Greenwald R A, Ramamurthy N S, Moak S A, Koszulinski R, Dieudonne D, Golub L M
Department of Chemistry, State University of New York/Old Westbury 11568, USA.
J Rheumatol. 1995 Sep;22(9):1726-31.
To identify a mechanism by which a matrix metalloproteinase (MMP) inhibitor might act synergistically with other agents to decrease MMP activity and thereby lessen the radiologic severity of adjuvant arthritis.
Rats with adjuvant arthritis were treated with either flurbiprofen (FBP) or tenidap (TDP), along with 4-dedimethylaminotetracycline (CMT-1), a potent MMP inhibitor. Indices of inflammatory severity and of radiologic destruction were assessed and compared to serum and bone levels of the MMP inhibitor.
Combination therapy with the MMP inhibitor plus either of the other drugs led to synergistic improvement in radiologic severity. For example, CMT-1 combined with TDP reduced radiologic severity 45% while decreasing collagenase and gelatinase activities by 61 and 72%, respectively, more than doubling bone CMT-1 levels (7.6 micrograms/g to 16.4 micrograms/g). FBP had similar effects.
MMP inhibitors need access to the arthritic joint to interact with their target enzymes. Concomitant antiinflammatory therapy is required to assure drug entry into the inflamed tissues.
确定基质金属蛋白酶（MMP）抑制剂可能与其他药物协同作用以降低MMP活性，从而减轻佐剂性关节炎放射学严重程度的机制。
给佐剂性关节炎大鼠分别用氟比洛芬（FBP）或替硝唑（TDP），以及一种有效的MMP抑制剂4-去二甲氨基四环素（CMT-1）进行治疗。评估炎症严重程度和放射学破坏指标，并与MMP抑制剂的血清和骨水平进行比较。
MMP抑制剂与其他任何一种药物联合治疗均导致放射学严重程度的协同改善。例如，CMT-1与TDP联合使用可使放射学严重程度降低45%，同时胶原酶和明胶酶活性分别降低61%和72%，骨CMT-1水平增加一倍多（从7.6微克/克增至16.4微克/克）。FBP也有类似效果。
MMP抑制剂需要进入关节炎关节才能与其靶酶相互作用。需要同时进行抗炎治疗以确保药物进入炎症组织。
