[Establishment of a model of reproductive system injury in male Wistar rats in high-altitude hypoxia environment].

OBJECTIVE: To establish a model of reproductive system injury in male rats at high altitude using the low-pressure hypoxic animal laboratory and study the changes in the testicular tissue, semen parameters, blood gas and oxidative stress in male rats at different altitudes. METHODS: Sixty male Wistar rats were randomly assigned to be raised on the plains (the plains group, n = 20), at an altitude of 4 000 m (the plateau model group Ⅰ, n = 20), or at an altitude of 6 000 m (the plateau model group Ⅱ, n = 20) for a spermatogenic cycle of 14 days. After establishment of the model of high-altitude reproductive system injury, the testis tissues of the rats were harvested for HE staining and observed for histopathological changes under the light microscope, and their epididymedes collected for preparation of sperm suspension and detection of sperm motility, sperm count and the percentage of morphologically abnormal sperm (MAS). The blood gas level and oxidative stress-related indexes in different groups were also measured using the serological test. RESULTS: With the elevation of altitude, the levels of pH and PO2 were decreased, those of PCO2, Hct, K+, Cl－ and Hb increased markedly, while that of Na+ exhibited no significant change. The model rats also showed folded spermatogenic tubule walls, thinned spermatogenic epithelia, disorderly arranged and reduced number of spermatogenic cells, and increased vascuolization in the spermatogenic epithelia, with decreased sperm motility and count, increased percentage of MAS, elevated concentration of malondialdehyde (MDA) and reduced activity of superoxide dismutase (SOD). CONCLUSIONS: A model of reproductive system injury was successfully established in male rats at a simulated altitude of 4 000 m. With increasing of the altitude to 6000 m, oxidative damage to the testicular tissue was aggravated, sperm motility decreased, and the percentage of MAS increased, indicating that an altitude of 6 000 m may cause serious damage to the rat reproductive system.

Experimental study on inhibitory effects of histone deacetylase inhibitor MS-275 and TSA on bladder cancer cells.

OBJECTIVE: To investigate the inhibitory effect of histone deacetylase (HDAC) inhibitors (MS-275 and TSA) on T24 human bladder cancer cells in vitro, and explore the possible mechanism. METHODS: The MTT assay was employed to evaluate the inhibitory effect of MS-275 and TSA on T24 cell growth. FCM was used to analyze the variation of T24 cell cycle distribution and the apoptotic ratio after T24 cells were treated with MS-275 and TSA. Histone acetylation level was detected by Western blot. mRNA expression of p21 WAF1/CIP1, cyclin A, and cyclin E was measured by FQ-PCR. Dynamic changes of Bcl-2 and bax expression were detected by FCM. RESULTS: MS-275 and TSA inhibited T24 cell growth in a concentration and time-dependent manner. Treatment with 4 µmol/l MS-275 or 0.4 µmol/l TSA blocked cell cycling in the G0/G1 phase and induced a significant increase in cell apoptosis. MS-275 and TSA significantly increased the level of histone acetylation, induced p21CIP1WAF1 mRNA expression, and inhibited cyclin A mRNA expression, though no significant effect was observed on cyclin E. Bcl-2 expression was down-regulated, while bax expression was up-regulated. CONCLUSION: HDAC inhibitors can block bladder cancer cell cycle in vitro and induce apoptosis. The molecular mechanism may be associated with increased level of histone acetylation, down-regulation of p21WAF1/CIP1 expression, up-regulation of cyclin A expression, and dynamic change of bcl-2 and bax expression.