اثرات پیشگیرانه سترورلیکس بر تغییرات ایجاد شده توسط سیسپلاتین بر سلولهای اسپرماتوژنیک، میوئید و بازال لامینای مجاری سمینیفر در بیضه موش نژاد Balb/C
محورهای موضوعی :
آسیب شناسی درمانگاهی دامپزشکی
داریوش محمد نژاد
1
,
جعفر سلیمانی راد
2
,
آمنه محمدی روشنده
3
1 - مرکز تحقیقات کار بردی دارویی، استادیار دانشگاه علوم پزشکی تبریز، تبریز، ایران
2 - گروه علوم تشریح، دانشکده پزشکی، استاد دانشگاه علوم پزشکی تبریز، تبریز، ایران
3 - گروه علوم تشریح، دانشکده پزشکی، استادیار دانشگاه علوم پزشکی همدان، همدان، ایران
تاریخ دریافت : 1391/06/25
تاریخ پذیرش : 1391/11/11
تاریخ انتشار : 1391/12/01
کلید واژه:
سیسپلاتین,
سترورلیکس,
اسپرماتوژنز,
سلول میوئید,
بازال لامینا,
چکیده مقاله :
سیسپلاتین به عنوان یک داروی موثر در شیمی درمانی می تواند اثرات سوء در اسپرماتوژنز داشته باشد. از طرف دیگر اسپرماتوژنز تحت تاثیر هورمون های گنادوتروپین (LH وFSH) می باشد. به نظر می رسد، موقع شیمی درمانی بتوان با سرکوب ترشح LH و FSH موجب توقف اسپرماتوژنز گردید و به این ترتیب این سلول ها را در برابر اثرات سوء سیسپلاتین حفظ کرد. سترورلیکس (آنتاگونیستGnRH ) برای توقف ترشح گنادوتروپین ها مورد استفاده قرار می گیرد. در این تحقیق سعی شده است توانایی داروی سترورلیکس در مهار اثرات سوء سیسپلاتین بر اپیتلیوم لایه ژرمینال بیضه بررسی گردد. در این مطالعه 30 سر موش نر بالغ 8-6 هفته ای Balb/C به طور تصادفی به 3 گروه 10تایی تقسیم شدند. گروه 1 به عنوان شاهد سالم در نظر گرفته شد و هیچ دارویی دریافت نکرد. گروه آزمایش 1 سیسپلاتین را روزانه به مقدار bw/ mg/kg5/2 به صورت داخل صفاقی به مدت 5 روز دریافت کرد. در گروه آزمایش 2 تزریق سترورلیکس هفته ای سه بار به صورت زیر جلدی هر بار به میزان mg/kg/bw 25/0 انجام شد که یک هفته قبل از تزریق سیسپلاتین شروع و در هفته های دوم (همراه با سیسپلاتین) و سوم نیز ادامه یافت. بعد ازگذشت 35 روز از آخرین تزریق از بیضه ها برای مطالعه هیستولوژی، هیستوشیمی و میکروسکوپ الکترونی نمونه برداری شد. نتایج توسط آزمون آنالیز واریانس یک طرفه و آزمون تعقیبی توکی مورد تحلیل آماری قرار گرفتند. نتایج هیستولوژی نشان داد که در گروه دریافت کننده سیسپلاتین هسته سلول های اسپرماتوگونی متراکم تر و قطر لوله های سمینی فر نسبت به گروه شاهد کاهش یافته است و در برخی از لوله ها فقط سلول های سرتولی مشاهده می شدند. مطالعه هیستوشیمیایی این گروه نشان داد که تعداد سلول های آپوپتوتیک در این گروه افزایش یافته است. مطالعه با میکروسکوپ الکترونی نیز نشان دهنده غشاء پایه موجی شکل و نامنظم لوله های سمینی فر به همراه سلول های میوئید ضخیم و در حال انقباض بود. در گروه آزمایش 2 سترورلیکس تا حدود زیادی اثرات سوء سیس پلاتین را مهار کرده بود. نتایج این مطالعه نشان داد تزریق سترورلیکس همراه با سیسپلاتین سلول های اسپرماتوژنیک را از اثرات سوء سیس پلاتین حفاظت می کند.
چکیده انگلیسی:
Cisplatin used in chemotherapy can have side effect on spermatogenesis. As it is known Gonadotropine hormones (LH, FSH) affect spermatogenesis. It seems by suppressing secretion of LH and FSH during chemotherapy, spermatogenesis could stopped which could result in protection of the cells from cisplatin side effects. The aim of the present study is to investigate the preventive effect of cetrorelix (GnRH antagonist) on spermatogenic defect produced by Cisplatin. In the present study thirty adult male mice aging 6-8 weeks were divided into 3 groups as: Control, Experimental 1 and Experimental 2. Experimental 1 received Cisplatin for 5 days as 2.5 mg/kg intraperitoneally and Experimental 2 received 0.25 mg/kg cetrorelix (GnRH antagonist) one week before cisplatin treatment and continued for 3 weeks. After 35 days from last injection, testicular specimens were removed and prepared for light and electron microscopic study. The data were analyzed using ANOVA (Tukey) in all 3 groups. Histological results showed that nucleus of spermatogonia cells were more condensed and diameter of seminiferous tubules were reduced, in the group which received cisplatin in comparison with the control group. Histochemical studies showed an increase of apoptotic cells in the group which received cisplatin. Electron microscopy showed that in Experimental 1 group basment membrane was morphologically irregular and wavey and Myoid cells were thickened and contracted, but in Experimental 2 group the condition was similar to the control group. These results showed that injection of cetrorelix with cisplatin can protect spermatogenic cells against the side effects of cisplatin.
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