اثرات مخرب سیتوکین‌های التهابی ناشی از اندوتوکسین بر عملکرد کبد و کلیه و نقش تعدیل‌کننده استروژن در شرایط زنده

نوع مقاله : مقاله پژوهشی

نویسنده

گروه داروسازی، مؤسسه فنی پزشکی / کرکوک، دانشگاه فنی شمالی، عراق

چکیده

هدف: یکی از محرک‌های قوی سیستم ایمنی ذاتی، اندوتوکسین یا لیپوپلی‌ساکارید (LPS) است. این محرک می‌تواند منجر به سندرم پاسخ التهابی سیستمیک (SIRS) شود و در نهایت ممکن است به شوک سپتیک منجر گردد. استروژن یک هورمون استروئیدی است که نقش مهمی در تولیدمثل ماده‌ها دارد و همچنین عملکردهای متعددی در سایر سیستم‌های بدن از جمله سیستم ایمنی ایفا می‌کند. هدف این مطالعه بررسی بیان ژن‌های TNF-α، IL-6، CCL2 و CCL3 در پاسخ به LPS بود. اهداف دیگر این مطالعه شامل ارزیابی تغییرات هیستولوژیکی و عملکردی در کلیه و کبد، اندازه‌گیری سطح سرمی سیتوکین‌های التهابی مانند TNF-α، IL-6 و MCP-1 و بررسی اثرات اواریکتومی (برداشتن تخمدان‌ها و در نتیجه کمبود استروژن) بر میزان آسیب اندام‌ها و پاسخ التهابی ناشی از LPS در موش‌های بالغ ماده ویستار سه ماهه بود.
مواد و روش‌ها: برای بررسی اثرات استروژن، اندوتوکسین‌ها و ترکیب آن‌ها، گروه‌های متعددی در آزمایش در نظر گرفته شدند. تمام آزمایش‌های آزمایشگاهی برای ارزیابی سیتوکین‌های التهابی، عملکرد کبد و کلیه و بیان ژن‌ها در آزمایشگاه‌های دانشکده دامپزشکی، دانشگاه القادسیه، عراق انجام شد. مطالعه شامل ۱۳۸ موش بالغ ماده ویستار (۳ ماهه) بود که در شش گروه اصلی تقسیم شدند (G1-Sham, G2-OVX, G3-LPS, G4-E2+LPS, G5-LPS+E2, and G6-E2)؛ هر گروه شامل ۲۳ موش بالغ ماده ویستار بود.
نتایج: نتایج این مطالعه تفاوت آماری معناداری (p<0.05) در سطح سرمی سیتوکین‌های التهابی TNF-α، IL-6 و MCP-1 نشان داد. علاوه بر این، کراتینین و اوره (عملکرد کلیه)، ALT و AST (عملکرد کبد) و بیان ژن‌های TNF-α، IL-6، CCL2 و CCL3 نیز بین موش‌های بالغ ماده ویستار سه ماهه مشاهده شد.
نتیجه‌گیری: مطالعه نشان داد که استروژن اثرات مضر سیتوکین‌های التهابی افزایش‌یافته به‌واسطه اندوتوکسین‌ها را کاهش می‌دهد و بنابراین عملکرد کبد و کلیه را در موش‌های بالغ ماده ویستار فعال می‌کند. مسیر سیگنالینگ استروژن می‌تواند یک هدف درمانی امیدوارکننده برای کاهش آسیب چنداندامی ناشی از سپسیس در شرایط کمبود استروژن باشد. پیش‌درمانی با استروژن بیان TNF-α را تقریباً 40% نسبت به گروه دریافت‌کننده تنها LPS کاهش داد.

کلیدواژه‌ها

عنوان مقاله [English]

Deleterious effects of inflammatory cytokines induced by endotoxin on hepato-renal functions and attenuating role of estrogen in vivo

نویسنده [English]

  • Ozdan Akram Ghareeb
Pharmacy Department, Medical Technical Institute / Kirkuk, Northern Technical University, Iraq
چکیده [English]

Objective
One of the potent innate immune system stimulators is endotoxin or lipopolysaccharide (LPS). This stimulator can lead to systemic inflammatory response syndrome (SIRS). It may also ultimately lead to septic shock. Estrogen is a steroid hormone that plays an important role in female reproduction. This hormone also has multiple roles in other body systems, including the immune system. The aim of this study was to investigate the expression of TNF-α, IL-6, CCL2 and CCL3 genes in response to LPS. Other aims of this study were to evaluate histological and functional changes in the kidney and liver, measure serum levels of inflammatory cytokines such as TNF-α, IL-6 and MCP-1, and investigate the effects of ovariectomy (removal of the ovaries and consequently estrogen deficiency) on the extent of organ damage and inflammatory response induced by LPS in three-month-old adult female Wistar rats.
Materials and methods
Several groups would typically be included in an experiment to examine the effects of estrogen, endotoxins, and their combination. All laboratory tests for assessing inflammatory cytokines, kidney and liver function, and gene expression were carried out in the laboratories of the College of Veterinary Medicine, Al-Qadisiyah University, Iraq. The study included 138 adult female Wistar rats (3 months old) distributed across six main groups; each set contains 23 adult female Wistar rats including G1-Sham, G2-OVX, G3-LPS, G4-E2+LPS, G5-LPS+E2, and G6-E2).
Results
The results of this study reported a statistically significant difference (p<0.05) in serum levels of inflammatory cytokines TNF-α, IL-6 and MCP-1. In addition, creatinine and urea (kidney function), ALT and AST (liver function) and TNF-α, IL-6, CCL2 and CCL3 gene expression were observed between 3-month-old female Wistar rats.

Conclusions
The study concluded that estrogen reduces the harmful effects of inflammatory cytokines that increase due to endotoxins, and therefore estrogen activates liver and kidney functions in adult female Wistar rats. Estrogen signaling may represent a promising therapeutic target for mitigating sepsis-induced multi-organ injury in estrogen-deficient states. Estrogen pre-treatment reduced TNF-α expression by ~40% relative to LPS-only group.

کلیدواژه‌ها [English]

  • endotoxin
  • estrogen
  • IL-6
  • inflammatory cytokines
  • TNF-α

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مجله بیوتکنولوژی کشاورزی
دوره 18، شماره 1
فروردین 1405
صفحه 259-280

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