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目的观察连续给予去甲斑蝥素-壳聚糖缓释制剂(NCTD-CTS)和去甲斑蝥素(NCTD)对大鼠长期毒性的损伤表现、程度及可逆性,为进一步的实验研究提供依据。方法 SD大鼠分为实验组(NCTD-CTS组)、阳性对照组(NCTD组)及空白对照组(给予等体积生理盐水),实验组和阳性对照组分为高、中、低3个剂量组,腹腔注射,连续12周(每天1次)。除观察一般状况外,检测体质量、血液生化学指标,重要脏器指数的变化,并进行常规病理检查,停药后,进行恢复期观察。结果相对于空白对照组,连续给予不同剂量的NCTD-CTS和NCTD均可导致大鼠体质量下降,饮食、饮水不佳。血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、尿素氮(BUN)、肌酐(CRE)活性均升高。NCTD-CTS组的肝脏指数均不同程度的升高,NCTD组的肝脏、肺和肾指数均有不同程度的升高,毒性损伤程度与给药剂量呈现一定的剂量依赖相关性,经过恢复期观察,部分病变不可逆。结论 NCTD-CTS和NCTD对大鼠长期毒性主要表现为肝、肺、肾脏的损伤,且部分病变为不可逆损伤,但NCTD-CTS对大鼠的长期毒性程度低于NCTD。
OBJECTIVE: To observe the long-term toxicity, extent and reversibility of NCTD-CTS and NCTD in rats, and to provide basis for further experimental study. Methods SD rats were divided into experimental group (NCTD-CTS group), positive control group (NCTD group) and blank control group (given equal volume of normal saline). Experimental group and positive control group were divided into three groups: high, middle and low dose Group, intraperitoneal injection for 12 weeks (once daily). In addition to observing the general situation, body mass, blood biochemical indicators, changes in vital organs index, and routine pathological examination, withdrawal, recovery period observation. Results Compared with the blank control group, continuous administration of different doses of NCTD-CTS and NCTD can lead to decreased body weight, poor diet and poor drinking water. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (CRE) activity were increased. The liver index of NCTD-CTS group increased to some extent, and the liver, lung and kidney index of NCTD group all increased to some extent. The degree of toxicity injury was dose-dependently dependent on the dose of NCTD-CTS. , Some lesions irreversible. Conclusion The long-term toxicity of NCTD-CTS and NCTD in rats is mainly manifested as liver, lung and kidney damage, and some lesions are irreversible damage. However, the long-term toxicity of NCTD-CTS in rats is lower than NCTD.