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。
PartⅠThe creation of experimental varicocele model in ratsand its feasibility on the model
Objective To study the methods of successful creation of experimental varicocele model, To evaluation its feasibility on the model, To study the effect of experimental varicocele on the testis in rats and investigate the mechanism of the infertility resulting from varicocele.
Materials and Methods A varicocele model was created by partial ligation of the left renal vein in rats. Six, nine and twelve weeks after creation of the vricocele, the histology of the testes was studied and the statistical analyse was made.
Results An experimental varicocele model was successfully induced by partially ligating the left renal vein in male rats. The main pathological changes in the testis of the model rats were degeneration of germinal epithelium, tubular atrophy and interstitial edema, and these lesions were bilateral and progressive with the over time. The statistical analyses showed that the numbers of degenerating tubules of the two sides for each varicocele group were significantly increased compared with those of the control group and its was progressive with over time. Its pathological characteristic were similar with the human varicocele.
Conclusions successful created the experimental left varicocele rat model. left varicocele rat has severe bilateral and progressive damaging effects on the testes, which may be the most important reason for infertility resulting from varicocele.
PartⅡVaricocele and retrograde adrenal metabolites flow
Objective On the basis of successful created experimental left varicocele rat model. To study the effects of adrenal metabolite reflux on the infertility induced by varicocele and investigate the mechanism of the infertility resulting from varicocele.
Materials and Methods In the study, 10 male SD adult rats, each weighing 270-300g, were used. The rats were subdivided into two groups of 5 rats. In group A, varicocele was induced by means of partial ligation of the left renal vein in rats in order to cause a renospermatic reflux (Reference PartⅠ). In group B, similarly to group A, varicocele was induced after ligation of the left adrenal vein. The effects of varicocele on the adrenal vascular anatomy, adrenal pathology, and the volume of renal of this condition were then analyzed 6 weeks after surgery. The adrenal vascular anatomy were compared with the anatomy to known patterns of vascular drainage from the human normal adrenal gland.
Results In groups A, The renal volume was normal, the kidney was atrophy in groups B.The adrenal pathology was similar in two groups. significant differences were found in the diameter of adrenal vein in group A and the normal rat [P <0.001]. The adrenal vasculature of the rat shares some important similar anatomical features with human anatomy.
Conclusions The adrenal vein shares the flow of the kidney and there is not the retrograde adrenal metabolites flow in the rat model. the retrograde adrenal metabolites flow is not the cause of the infertility induced by varicocele.
PartⅢExpression and Significance of Notch 1 in thenormal and experimental left varicocele rat
Objective To study expressions of Notch 1 in normal and varicocele - induced rat testes to examine their possible functions in cell fate. and analyzed the mechanism of the infertility resulting from varicocele.
Materials and Methods The control group underwent a sham operation (n= 5). The experimental groups underwent partial ligation of the renal vein to induce an experimental varicocele and then were killed 6 (n= 5), 9 (n =5), and 12(n= 5) weeks after the induction of varicocele. Partial tissues were fixed and routinely processed for paraffin embedding. Subsequent immunohistochemical studies were performed. Partial tissues were frozed in refrigeratory and Subsequent Westen-bloting studies were performed.
Results In the sham-operation rat testes, spermatogonia and primary spermatocytes cells were immunopositive and Leydig cells were immunonegitive for Notch 1. Varicocele formation diminished the expression of Notch-1 as the varicocele formation progressed over time. the degree of diminished expression was similar at two sides. Significant differences were found in groups.
Conclusions The present study suggests that Notch 1 is related to the proliferation, differentiation, and apoptotic processes of spermatogonia. The decrease of Notch-1 expression depended on the degree of varicocele development over time, indicating a potential role in varicocele-associated testicular dysfunction.
引文
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1.World Health Organisation.The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics.Fertil Steril 1992;57:1289-1293.
2.Greenberg SH.Varicocele and male infertility.Fertil Steril 1977;28:699-706.
3.Ahlberg NE,Bartley O,Chidekel N.Right and left gonadal veins.An anatomical and statistical study. Acta Radiol Diagn 966;4:593-601.
4. Coolsaet BL. The varicocele syndrome: venography determining the optimal level for surgical management. J Urol 1980;124:833-839.
5. Derya T, Ergin K , Robert T, et al. The Complex Structure of the Smooth Muscle Layer of Spermatic Veins and Its Potential Role in the Development of Varicocele Testis. European urology 2007 51:1402 - 1410.
6. 郭宏骞,孙则禹.吴阶平泌尿外科学.济南:山东科学技术出版社,2004. 1951-1952.
7. Green KF, Turner TT, Howards SS. Varicocele: reversal of the testicular blood flow and temperature effects by varicocele repair. J Urol 1984;131:1208-1211.
8. Sigman M, Jarow JP. Male infertility. In: Walsh PC, Retik AB, Vaughn ED et al (eds). Campbell's Urology 8th edn. Philadelphia:Saunders,2002: 1475-1532.
9. Yamaguchi M, Sakatoku J, Takihara H. The application of intrascrotal deep body temperature measurement for the noninvasive diagnosis of varicoceles. Fertil Steril 1989;52:295-301.
10. Zorgniotti AW, Macleod J. Studies in temperature, human semen quality, and varicocele. Fertil Steril. 1973;24:854-863.
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