精索静脉曲张大鼠模型的建立及其不育发生机理的实验研究
发布时间:2018-07-03 04:32
本文选题:大鼠 + 实验性精索静脉曲张 ; 参考:《中国协和医科大学》2008年博士论文
【摘要】: 第一部分:大鼠实验性精索静脉曲张模型的建立及其可行性评价 【目的】探讨成功建立实验性左侧精索静脉曲张动物模型的方法,研究精索静脉曲张大鼠对睾丸的损害,评价模型用于实验研究的可行性,探讨精索静脉曲张不育的机理。 【方法】通过部分结扎左肾静脉建立大鼠实验性精索静脉曲张(ELV)模型,分别于术后6周和9周和12周研究双侧睾丸的组织学改变并进行统计学分析。 【结果】该模型大鼠的睾丸病理损害以生精上皮退化,精子发生阻滞,生精细胞脱落,曲精小管萎缩,间质水肿最为多见,损害为双侧性,统计学分析显示,ELV大鼠左右侧睾丸曲细精管退化百分比较对照组增加,病变有时间累进性特点,与人类睾丸的病理损害具有相似性。 【结论】成功建立了ELV模型,该模型为研究精索静脉曲张的病理生理改变提供了有用工具。ELV大鼠双侧睾丸有严重的累进性病理改变,这可能是精索静脉曲张不育的主要原因之一。 第二部分:左侧精索静脉曲张与肾上腺代谢产物返流 【目的】在成功建立大鼠实验性左侧精索静脉曲张模型的基础上,探讨实验性大鼠左侧精索静脉曲张与肾上腺代谢产物返流的关系,进一步探讨肾上腺代谢产物返流在精索静脉曲张不育发生机理中的作用。 【方法】10只成年雄性SD大鼠,每只体重量为270—300克,随机分为2组,每组5只,A组通过部分结扎肾静脉建立实验性精索静脉曲张模型;B组在建立左侧精索静脉曲张模型的基础上,结扎肾上腺静脉,模型建立6周后观察二组模型大鼠肾上腺静脉直径、肾脏和肾上腺病理变化;并比较大鼠和人类肾上腺静脉解剖,了解二者之间的相似性。 【结果】A组大鼠肾脏体积无明显变化,成功建立了ELV大鼠模型,B组大鼠肾脏全部萎缩,B组肾上腺静脉与A组相比明显增粗,二组比较具有统计学意义。二组大鼠肾上腺病理比较无明显差异。大鼠肾上腺静脉解剖与人类相比,有很大的相似性,除肾上腺静脉以外,存在膈下静脉交通。 【结论】实验性精索静脉曲张大鼠肾上腺静脉成为肾脏静脉血流分支之一,不存在肾上腺代谢产物返流;肾上腺代谢产物返流不是精索静脉曲张不育的原因。 第三部分:Notch 1蛋白在正常和左侧精索静脉曲张模型大鼠睾丸中的表达及其意义 【目的】探讨Notch 1蛋白在正常和左侧精索静脉曲张模型大鼠睾丸中的表达及其在精子发生过程中的作用,进一步了解Notch 1在精索静脉曲张不育发生机理中的作用。 【方法】应用第一部分中成功建立的大鼠ELV模型睾丸标本(假手术组、6周组、9周组、12周组)一部分应用于免疫组化研究,冻存部分应用Westenbloting方法检测Notch 1表达水平。采用单因素方差分析和显著性检验进行统计学分析。 【结果】在睾丸生精小管中,Notch 1主要表达于精原细胞和初级精母细胞胞质内,而在支持细胞内未见阳性表达;精原细胞表达为强阳性。精索静脉曲张引起Notch 1在双侧睾丸中表达减少,并有时间累进性的特点,组间比较具有统计学意义。 【结论】Notch 1蛋白可能参与精原细胞分化,增值过程,ELV引起累进性Notch 1表达减少,可能是VC导致不育的重要原因之一。
[Abstract]:Part one: establishment of rat experimental varicocele model and its feasibility evaluation.
[Objective] to explore the method of establishing experimental left spermatic varicocele animal model, study the damage of spermatic varicose rat to testis, evaluate the feasibility of the model in experimental study, and explore the mechanism of sterility of varicocele.
[Methods] the experimental varicocele (ELV) model of rats was established by partial ligation of the left renal vein. The histological changes of bilateral testicles were studied at 6, 9 and 12 weeks after the operation, and the statistical analysis was performed.
[results] the pathological damage of the rat testis in this model was the degeneration of the spermatogenic epithelium, the block of spermatogenesis, the exfoliation of spermatogonia, the atrophy of the seminiferous tubules, the most common interstitial edema, and the bilateral damage. The statistical analysis showed that the degeneration of the testicular seminiferous tubules in the left and right sides of the ELV rats was increased compared with the control group, and the pathological changes had time progressive characteristics, The pathological damage of human testicles is similar.
[Conclusion] the ELV model has been successfully established. This model provides a useful tool for the study of the pathophysiological changes of varicocele. The bilateral testicles of.ELV rats have serious progressive pathological changes, which may be one of the main reasons for the sterility of varicocele.
The second part: left varicocele and adrenal metabolite reflux.
[Objective] to explore the relationship between the left spermatic varicocele and adrenalic reflux in experimental rats on the basis of the successful establishment of experimental left spermatic varicocele model in rats, and to further explore the role of adrenalic reflux in the mechanism of spermatic varicocele infertility.
[Methods] 10 adult male SD rats, each body weight of 270 to 300 grams, were randomly divided into 2 groups, each group was 5. The A group established the experimental varicocele model by partial ligature of the renal vein. Group B was established on the basis of the left spermatic varicocele model and ligated the adrenal vein, and the model was established to observe the adrenal adrenal gland of two groups of rats after 6 weeks. The diameter of vein, the pathological changes of kidney and adrenal glands, and the anatomy of the adrenal veins between rats and human beings were compared to understand the similarity between the two.
[results] there was no obvious change in kidney volume in the A group. The ELV rat model was successfully established. The kidneys of group B rats were all atrophied. The adrenal vein in group B was significantly thicker than that in A group. The two groups were statistically significant. There was no significant difference in the pathology of adrenal glands in the two groups. The anatomy of the suprarenal gland vein was similar to that of the human. In addition to the adrenal vein, there is a subphrenic vein traffic.
[Conclusion] the adrenal vein of experimental varicocele is one of the branches of renal venous blood flow, and there is no reflux of adrenalic metabolites, and adrenalic reflux is not the cause of sterility of varicocele varicocele.
The third part: the expression and significance of Notch 1 protein in the testis of normal and left varicocele rats.
[Objective] to investigate the expression of Notch 1 protein in the testis of normal and left spermatic varicocele model rats and its role in the process of spermatogenesis, and to further understand the role of Notch 1 in the mechanism of sterility of varicocele.
[Methods] the testicular specimens of rat ELV model (sham operation group, 6 week group, 9 week group, 12 week group) were applied to immunohistochemical study in part one, and the expression level of Notch 1 was detected by Westenbloting method. The statistical analysis was carried out by single factor analysis of variance and significant test.
[results] in the testicular seminiferous tubules, Notch 1 was mainly expressed in the cytoplasm of spermatogonial and primary spermatocyte, but no positive expression in the supporting cells. The expression of spermatogonial cells was strong positive. The expression of Notch 1 in the spermatic vein decreased in bilateral testicles and had the characteristics of progressive time. The comparison of the groups was statistically significant.
[Conclusion] Notch 1 protein may be involved in the differentiation of spermatogonial cells, the increment process, and the decrease of progressive Notch 1 expression caused by ELV, which may be one of the important reasons for the infertility caused by VC.
【学位授予单位】:中国协和医科大学
【学位级别】:博士
【学位授予年份】:2008
【分类号】:R697.24;R-332;R698.2
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