Guimarães S A, Akatsu T, Tago E M, Consolaro A
Department of Pathology, School of Dentistry of Bauru, University of São Paulo, Brazil.
Inflammation. 1996 Dec;20(6):623-36. doi: 10.1007/BF01488800.
A purified bacterial cell walls suspension from human dental plaque were biochemically prepared to serve as flogogenous agent in producing experimental inflammatory models in rats. In the vascular permeability inhibition assay (edemogenic test), the subcutaneous implantation of the flogogenous agent elicited an acute inflammatory reaction highly susceptible to the effects of the non-steroidal anti-inflammatory drugs (NSAIDs). The intradermal injection of the flogogenous agent in the dorsum of rats developed experimental granulomas also susceptible to the anti-inflammatory effects of the NSAIDs. Otherwise, the antimitotic effect of drugs was carried out in the model of cellular proliferation of duodenal mucosa of rats by incorporation of tritiated thymidine (3H TdR) in the DNA. These models of acute and chronic inflammation, and the antimitotic model permitted us to evaluate the anti-inflammatory and antimitotic effects of sulindac, ibuprofen, naproxen and glucametacin. In the antiexudative activity, evaluated by the edemogenic test, naproxen was the more effective drug followed by sulindac, ibuprofen and glucametacin (in a decreasing order of potency) to inhibit the exudative response induced by the bacterial cell walls suspension, in all experimental periods. In the chronic anti-inflammatory activity, evaluated by the granuloma inhibition assay, all drugs were capable to demonstrate effectiveness against the development of the experimental granulomas induced by an intradermal injection of the flogogenous agent. In the model of cellular proliferation, all tested drugs demonstrated antimitotic activity in all experimental periods (4, 6 and 8 days), also. Sulindac induced the higher antimitotic effect, in all experimental periods, followed by ibuprofen, naproxen and glucametacin in a decreasing order of efficacy. There was a positive correlation between the antiexudative, anti-proliferative, and antimitotic effects.
从人牙菌斑中生物化学制备纯化的细菌细胞壁悬液,用作在大鼠中产生实验性炎症模型的致炎剂。在血管通透性抑制试验(致水肿试验)中,皮下植入致炎剂引发了对非甾体抗炎药(NSAIDs)作用高度敏感的急性炎症反应。在大鼠背部皮内注射致炎剂可形成实验性肉芽肿,其也对NSAIDs的抗炎作用敏感。此外,通过将氚标记的胸腺嘧啶核苷(3H TdR)掺入DNA,在大鼠十二指肠黏膜细胞增殖模型中进行药物的抗有丝分裂作用研究。这些急性和慢性炎症模型以及抗有丝分裂模型使我们能够评估舒林酸、布洛芬、萘普生和葡甲胺的抗炎和抗有丝分裂作用。在通过致水肿试验评估的抗渗出活性方面,在所有实验阶段,萘普生是抑制细菌细胞壁悬液诱导的渗出反应最有效的药物,其次是舒林酸、布洛芬和葡甲胺(效力递减)。在通过肉芽肿抑制试验评估的慢性抗炎活性方面,所有药物都能够证明对皮内注射致炎剂诱导的实验性肉芽肿的发展有效。在细胞增殖模型中,所有受试药物在所有实验阶段(4、6和8天)也都表现出抗有丝分裂活性。舒林酸在所有实验阶段诱导的抗有丝分裂作用最强,其次是布洛芬、萘普生和葡甲胺,效力递减。抗渗出、抗增殖和抗有丝分裂作用之间存在正相关。