Objective To evaluate the effect of propofol on lung cell apoptosis induced by acute pulmonary thromboembolism (APTE) .Methods Forty male SD rats weighing 280-300 g were randomly divided into 5 groups ( n = 8 each) : group Ⅰ sham operation ( group S) ; group ⅡAPTE and 3 propofol groups ( group P1-3). APTE was produced by iv injection of auto-blood clots. Venous blood 0.2 ml was obtained from rat tail vein and placed in a sterile test tube which was kept in water bath at 37 ℃ overnight. The blood clot was cut into thrombi ( diameter 1 mm, length 5 mm) the next day. Fifteen thrombi in 2 ml of normal saline were injected into immediately after iv injection of auto-bloed clots. The animals were killed at the end of 4 h propofol infusion and lung specimens were obtained for determination of lung cell apoptosis rate by flow eytometry and expression of caspase-3, Bax, Bcl-2, Fas, FasL mRNA and protein by RT-PCR and Western blot.The expression of Bcl-2/Bax mRNA and protein was calculated. Results Compared with group S,APTE significantly increased the lung cell apoptosis rate, and expression of caspase-3, Bax, Fas, FasL and decreased the expression of Bcl-2 and Bcl-2/Bax. Propofol infusion significantly attenuated these APTE-induced changes. Conclusion Propofol can inhibit APTE-induced lung cell apoptosis by down-regulating the caspase-3, Fas and FasL expression and regulating the balance between Bcl-2 and Bax expression.

There are some shortcomings of animal experiments applied in chemical toxicity testing, such as long period, large cost, species differences and dose differences, which limit the use of animal experiments' results in predicting human toxicity.Accordingly, we established a toxicity testing alternative screening system in line with the toxicity endpoints which required in chemical safety evaluation and risk assessment (genotoxicity, carcinogenicity, reproductive toxicity, acute toxicity and general toxicity) based on 3R principles (replacement, reduction, refinement) for animal experiments.This system covers most of the endpoints of toxicity assessment, and molecular biology technology was also applied to integrate the toxicity test, as well as some operation was optimized in order to shorten the experimental period, reduce experimental costs, improve animal welfare.Furthermore, the results from the screening system have higher clinical relevance because it is based on the toxicity mechanisms.

In view of the characteristics of the computerized system,the key points in the quality assurance (QA) of the computerized system was discussed and summarized combined with the requirements of the GLP laboratory in Europe and America.The validation of computerized system,the control during the use of computerized system,period maintenance and safety protection of computerized system,archives of electronic data was discussed,expecting to provide reference for the management of computerized system in Chinese GLP laboratory which is generally not high currently.The experiences were obtained as follow:Through repeated inspection and review,the problem was found and set as the risk point;a targeted QA inspection plan was made focusing on the risk-based inspection and the QA inspection plan was timely adjusted according to the problems,which ensures the pertinence and validity of the QA inspection.