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目的:建立细菌脂多糖(lipopolysaccharide,LPS)缓释所致大鼠持续发热的模型。方法:制备LPS浓度为0.01～2mg/ml的胶原水凝胶,固化后以生理盐水浸泡,基质显色法测定LPS的日释放量,研究其体外释放过程;大鼠皮下注射LPS含量为0.02～4mg的胶原水凝胶,测定12d内肛温,研究LPS皮下缓释对大鼠体温的影响。大鼠皮下注射LPS含量为2mg的胶原水凝胶,分别于注射后2、8h及1、3、12d测定其血浆中肿瘤坏死因子α(TNF-α)浓度和肺组织中胞浆型磷脂酶A2α(cPLA2α)浓度,研究其对发热及炎性肺损伤相关细胞因子的影响。结果:LPS载入胶原水凝胶后可在12d内持续释放,除首日释放量高于次日约30～50%外,日释放量相对稳定,且与载入量呈正相关;大鼠皮下注射载LPS的胶原水凝胶后可出现不同程度和过程的发热,其中0.02、0.2mg组仅出现一过性发热,而2、4mg组尚可观察到持续12d的发热反应;发热过程中血液TNF-α浓度和肺组织cPLA2α浓度均有不同程度升高。结论:采用载LPS胶原水凝胶皮下注射可复制大鼠持续发热模型,可作为复制不同阶段温病-炎性肺损伤大鼠模型的基础。
Objective: To establish a model of persistent fever caused by sustained release of lipopolysaccharide (LPS) in rats. Methods: The collagen hydrogels with LPS concentration of 0.01 ~ 2mg / ml were prepared and immersed in physiological saline after curing. The daily release of LPS was determined by matrix colorimetry. The release of LPS was investigated in vitro. 4mg of collagen hydrogel, rectal temperature measured within 12d to study the sustained release of LPS on rat body temperature. Rats were subcutaneously injected with collagen hydrogel with an LPS content of 2 mg. The levels of tumor necrosis factor-α (TNF-α) in plasma and the levels of cytosolic phospholipase in lung tissue were measured at 2, 8, A2α (cPLA2α) concentrations, to study their effects on fever and inflammatory cytokines related to lung injury. RESULTS: LPS loaded collagen hydrogel sustained release within 12 days, except for the first day of release higher than the next day about 30 ~ 50%, the daily release was relatively stable, and the load was positively correlated; subcutaneous Injecting LPS-loaded collagen hydrogel, there were different degrees and process of fever, 0.02,0.2 mg group only had transient fever, and 2,4 mg group can still be observed for 12 days of fever reaction; fever during the blood TNF-αconcentration and lung tissue cPLA2αconcentration increased to varying degrees. CONCLUSION: Subcutaneous injection of LPS-loaded hydrogel can replicate the rat model of persistent fever and can be used as a basis for replicating the rat model of warm-inflammation-induced lung injury in different stages.