Objective To investigate the effect of botulinum toxin type A (BTX- A) on the expression of HIF- 1a and VEGF in rat prostatic tissues of hyperplasia. Methods Sixty Wistar rats were randomly divided into experimental (n=45) and control (n=15) groups. Orchietectomy was performed in experimental group and androgen 4mg·kg-1·d-1 was administrated; the sham operation was performed in control group and liver oil was given instead. Five rats were sacrificed in each group to observe the hyperplasia in prostate glands after 1 week. Different doses of BTX- A were injected in the prostate of the castrated rats in H- dose (10U/0.1ml, n=10), M- dose (6U/0.1ml, n=10), L- dose (2U/0.1ml, n=10) and NS (NS/0.1ml, n=10) groups. After 4 weeks rats were sacrificed and the prostate glands were taken for weighting, the expression of HIF- 1α and VEGF were analyzed by immunohistochemical technique. Results The HIF- 1αdetected in cytoplasm and nucleus, especial y around the new vessels, the VEGF was detected only in cytoplasm. The weight of prostate in 4 experimental groups were significant higher than that in control group (P<0.05). The positive rate and grey value of HIF- 1αand VEGF in H- , M- and L- dose groups and VEGF in NS group were significantly higher than those in control group (P<0.05). The positive rate and grey values of HIF- 1αand VEGF in H- , M- and L- dose groups were significantly higher than those in NS group (P<0.05). There were also significant differences in positive rate and grey values of HIF- 1αand VEGF among H- , M- and L- dose groups (P<0.05). The HIF- 1αexpression was closely correlated with VEGF expression (r=0.575, P<0.01). Conclusion BTX- A can regulate the expression of HIF- 1α and VEGF of prostatic tissues, resulting in the inhibition of vascularization and attenuating hyperplasia of prostate gland.%目的：探讨A型肉毒毒素（BTX- A）对大鼠前列腺增生组织中缺氧诱导因子-1α（HIF-1α）和血管内皮细胞生长因子（VEGF）表达的影响。方法取60只大鼠，实验组45只，空白对照组15只。实验组大鼠均制作前列腺增生模型，1周后两组均随机处死5只大鼠观察建模是否成功。实验组剩余大鼠随机分为高剂量组（注射10U/0.1ml BTX- A）、中剂量组（注射6U/0.1ml BTX- A）、低剂量组（注射2U/0.1ml BTX- A）、阴性对照组（注射0.1ml0.9%氯化钠溶液），术后各组继续给予长效雄激素（十一酸睾酮针4mg· kg-1·d-1）维持，空白对照组仍给予等量橄榄油皮下注射。4周后处死各组大鼠，取出前列腺称重，免疫组化法检测比较各组大鼠前列腺组织中HIF-1α和VEGF的表达情况。结果大鼠前列腺增生模型建立成功。实验组大鼠HIF-1α在细胞质与细胞核均有表达，在新生血管周围表达明显增强，而VEGF的表达主要在细胞质中。与空白对照组比较，其他各组大鼠前列腺湿重均发生明显变化，差异均有统计学意义（均P＜0.05）；与阴性对照组比较，低、中、高剂量组大鼠前列腺湿重均发生明显增加，差异均有统计学意义（均P＜0.05）。空白组及阴性对照组均未见HIF-1α的表达；与空白对照组比较，高、中、低剂量组VEGF及HIF-1α的阳性表达率及灰度值、阴性对照组VEGF灰度值均发生明显变化（均P＜0.05）；与阴性对照组比较，中、低剂量组VEGF及HIF-1α的阳性表达率和高、中、低剂量组VEGF及HIF-1α的灰度值均发生明显变化（均P＜0.05）；与低剂量组比较，高、中剂量组VEGF及HIF-1α的阳性表达率及灰度值均发生明显变化（均P＜0.05）；与中剂量组比较，高剂量组VEGF的阳性表达率及灰度值和HIF-1α的阳性表达率均发生明显变化（均P＜0.05）。实验组大鼠HIF-1α与VEGF的表达呈明显正相关关系（r=0.575，P＜0.01）。结论前列腺内注射BTX- A可以通过抑制HIF-1α和VEGF的表达，从而抑制前列腺组织的血管形成，促使前列腺缩小。
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