新合成季铵盐单体化合物的体外抗菌和体内抗炎活性

Antibacterial activity in vitro and anti-inflammatory action in vivo of new quaternary ammonium salt monomer compounds

目的:观察新合成的4个季铵盐单体化合物的体外抗菌和体内抗炎活性。方法:将合成的4种季铵盐单体分别配制成高、中、低剂量的液体和固体制剂。检测其液体制剂对金黄色葡萄球菌、大肠杆菌及沙门菌的体外抗菌活性。用家兔对筛选出的化合物进行皮肤刺激性实验。将涂抹和未涂抹化合物的普通导尿管放置于家兔尿道5、10、15 d后,ELISA法测定家兔血浆中IL-10和TNF-α水平;放置15 d后HE染色观察尿道炎症细胞的生成情况。结果:体外抗菌活性测定结果显示,化合物2和4对3种细菌均有较好的抑制作用(P<0.05),而化合物1和3对3种细菌的抑制作用不明显。皮肤刺激性实验结果显示,化合物2和4对家兔皮肤均无刺激性;同一时间点,化合物2和4组家兔血浆IL-10水平明显高于对照组,而TNF-α水平明显低于对照组(P<0.05);HE染色结果显示,化合物2和4组家兔尿道黏膜组织中炎症细胞数及其浸润能力均低于对照组。结论:季铵盐单体化合物2和4具有较好的体外抗菌活性和体内抗炎活性。

Aim： To observe the activities of antibacterial in vitro and anti-inflammation in vivo of 4 kinds of synthesized quaternary ammonium salt monomer compounds. Methods： The liquid preparation and solid preparation at high,medium and low concentration of the four compounds were prepared,and their antibacterial activity against Staphylococcus aureus,Escherichia coli and Salmonella were tested using the liquid preparations. The irritated effects were investigated on normal skin of rabbits. The common catheters smeared with the compounds were placed into the rabbit urethra for 5,10,15 d,then the plasma levels of IL-10 and TNF-α were determined by ELISA,and the production of urethritis cells were investigated by HE staining method on the 15 th day. The rabbits with common catheter were the control. Results： Compound 2 and Compound 4 had better inhibitory effects on the three kinds of urethral flora（ P〈0. 05）,while Compound 1 and Compound 3 had no obvious inhibitory effect. Compound 2 and 4 had no irritated effect on the rabbit skin. The plasma level of IL-10 of Compound 2 and 4 groups was higher,and that of TNF-α was lower than the control group（ P〈0. 05）. The result of HE stainning showed that the number of inflammatory cells and the infiltration ability in Compound 2 and 4 groups were lower than the control group. Conclusion： Compound 2 and Compound 4 may have good activities of antibacterial in vitro and anti-inflammation in vivo.