MINOCYCLINE REDUCES GINGIVAL COLLAGENOLYTIC ACTIVITY DURING DIABETES - PRELIMINARY-OBSERVATIONS AND A PROPOSED NEW MECHANISM OF ACTION
MINOCYCLINE REDUCES GINGIVAL COLLAGENOLYTIC ACTIVITY DURING DIABETES - PRELIMINARY-OBSERVATIONS AND A PROPOSED NEW MECHANISM OF ACTION
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DOI：
10.1111/j.1600-0765.1983.tb00388.x
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发表时间：
1983-01-01
影响因子：
3.5
通讯作者：
RAMAMURTHY, NS
中科院分区：
文献类型：
--
作者：
GOLUB, LM;LEE, HM;RAMAMURTHY, NS
糖尿病会增加牙龈胶原酶活性，这种作用可能是由内源性组织变化介导的，并因牙龈缝隙中革兰氏阴性微生物的过度生长而加剧。为了扭转这种胶原溶解异常，对糖尿病大鼠和人类施用了适当的抗生素米诺环素（半合成四环素）。成年雄性常规或无菌大鼠用链脲佐菌素制成糖尿病，其中一半动物在处死前通过管饲给予米诺环素（20毫克/天）3-4周。解剖颊牙龈、整个皮肤和下颌骨并分别测试胶原蛋白溶解酶活性、胶原蛋白含量和牙槽骨损失。在一项初步研究中，将米诺环素（200 毫克/天）给予胰岛素依赖性糖尿病青少年和成年非糖尿病人 7 天；糖尿病患者的双胞胎兄弟接受了青霉素治疗。在抗生素治疗之前和之后，对每个受试者的 8 个牙周袋中的牙龈液胶原酶活性进行了测量（在新的微量测定中使用 [3H-甲基] 胶原作为底物）。还通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳和荧光照相法检查胶原酶消化产物。在大鼠中，米诺环素治疗：即使在无菌条件下，也能抑制糖尿病大鼠牙龈中异常升高的胶原蛋白溶解酶活性；在体外抑制多形核白细胞胶原酶活性，添加 Ca2+ 离子可逆转这种作用（青霉素-链霉素对该酶的活性没有影响）；并延缓糖尿病大鼠皮肤胶原蛋白和牙槽骨的异常损失。在一项针对人类的初步研究中，米诺环素疗法降低了龈沟液中的胶原酶活性，而青霉素则没有产生这种作用。显然，四环素治疗通过至少部分与其抗菌功效无关的机制抑制组织胶原蛋白溶解酶活性，并且该机制可能提供一种新的治疗方法来抑制牙周病期间发生的以及其他病理状况期间可能发生的过度胶原吸收。
Diabetes increases gingival collagenase activity, an effect that may be mediated by endogenous tissue changes and exacerbated by an overgrowth of gram-negative organisms in the gingival crevice. In an attempt to reverse this collagenolytic abnormality, an appropriate antibiotic, minocycline (a semisynthetic tetracycline), was administered to diabetic rats and humans. Adult male conventional or germfree rats were made diabetic with streptozotocin, and half of these animals were administered minocycline (20 mg/day) by tube feeding for 3-4 wk prior to sacrifice. The buccal gingiva, entire skins and mandibles were dissected and tested for collagenolytic enzyme activity, collagen content and alveolar bone loss, respectively. In a preliminary study, minocycline (200 mg/day) was administered for 7 days to an insulin-dependent diabetic adolescent human and an adult non-diabetic human; the twin brother of the diabetic was treated with penicillin. Gingival fluid collagenase activity was measured (using [3H-methyl] collagen as substrate in a new microassay) in 8 periodontal pockets in each subject before and after antibiotic therapy. Examination of collagenase digestion products by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography was also carried out. In rats, minocycline treatment: suppressed the abnormally elevated collagenolytic enzyme activity in gingiva of diabetic rats, even under germfree conditions; inhibited polymorphonuclear leukocyte collagenase activity in vitro, an effect that was reversed by the addition of Ca2+ ions (penicillin-streptomycin had no effect on the activity of this enzyme); and retarded the abnormal loss of skin collagen and alveolar bone in diabetic rats. In a preliminary study on humans, minocycline therapy reduced the collagenase activity of gingival crevicular fluid, an effect not produced by penicillin. Evidently, tetracycline therapy inhibits tissue collagenolytic enzyme activity by a mechanism at least in part unrelated to its antibacterial efficacy, and this mechanism may provide a new therapeutic approach for suppressing excessive collagen resorption which occurs during periodontal disease and which can occur during other pathologic conditions.