Erbatur Meral Erdal, Sezen Şaban Cem, Bayraktar Aslıhan Cavunt, Arslan Mustafa, Kavutçu Mustafa, Aydın Muhammed Enes
a Department of Anesthesiology and Reanimation , Gazi University , Ankara , Turkey.
b Department of Histology and Embryology , Kırıkkale University , Kırıkkale , Turkey.
Libyan J Med. 2017 Dec;12(1):1270021. doi: 10.1080/19932820.2017.1270021.
The aim of this study was to investigate whether dexmedetomidine - administered before ischemia - has protective effects against lower extremity ischemia reperfusion injury that induced by clamping and subsequent declamping of infra-renal abdominal aorta in streptozotocin-induced diabetic rats.
After obtaining ethical committee approval, four study groups each containing six rats were created (Control (Group C), diabetes-control (Group DM-C), diabetes I/R (Group DM-I/R), and diabetes-I/R-dexmedetomidine (Group DM-I/R-D). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd hour were accepted as diabetic. At the end of four weeks, laparotomy was performed in all rats. Nothing else was done in Group C and DM-C. In Group DM-I/R, ischemia reperfusion was produced via two-hour periods of clamping and subsequent declamping of infra-renal abdominal aorta. In Group DM-I/R-D, 100 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia period. At the end of reperfusion, period biochemical and histopathological evaluation of renal tissue specimen were performed.
Thiobarbituric acid reactive substance (TBARS), Superoxide dismutase (SOD), Nitric oxide synthase (NOS), Catalase (CAT) and Glutathion S transferase (GST) levels were found significantly higher in Group DM-I/R when compared with Group C and Group DM-C. In the dexmedetomidine-treated group, TBARS, NOS, CAT, and GST levels were significantly lower than those measured in the Group D-I/R. In histopathological evaluation, glomerular vacuolization (GV), tubular dilatation (TD), vascular vacuolization and hypertrophy (VVH), tubular cell degeneration and necrosis (TCDN), tubular hyaline cylinder (THC), leucocyte infiltration (LI), and tubular cell spillage (TCS) in Group DM-I/R were significantly increased when compared with the control group. Also, GV, VVH, and THC levels in the dexmedetomidine-treated group (Group DM-I/R-D) were found significantly decreased when compared with the Group DM-I/R.
We found that dexmedetomidine - 100 μg/kg intraperitoneally - administered 30 minutes before ischemia in diabetic rats ameliorates lipid peroxidation, oxidative stress, and I-R-related renal injury. We suggest that dexmedetomidine administration in diabetic rats before I/R has renoprotective effects.
本研究旨在探讨在链脲佐菌素诱导的糖尿病大鼠中,缺血前给予右美托咪定是否对肾下腹主动脉夹闭及随后松开所诱导的下肢缺血再灌注损伤具有保护作用。
获得伦理委员会批准后,创建了四个研究组,每组包含六只大鼠(对照组(C组)、糖尿病对照组(DM-C组)、糖尿病缺血/再灌注组(DM-I/R组)和糖尿病缺血/再灌注-右美托咪定组(DM-I/R-D组))。在糖尿病组中,腹腔注射单剂量(55mg/kg)链脲佐菌素。在第72小时血糖水平高于250mg/dl的大鼠被视为糖尿病大鼠。四周结束时,对所有大鼠进行剖腹手术。C组和DM-C组未做其他处理。在DM-I/R组中,通过夹闭并随后松开肾下腹主动脉两小时来产生缺血再灌注。在DM-I/R-D组中,在缺血期前30分钟腹腔注射100μg/kg右美托咪定。再灌注期结束时,对肾组织标本进行生化和组织病理学评估。
与C组和DM-C组相比,DM-I/R组的硫代巴比妥酸反应物质(TBARS)、超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)、过氧化氢酶(CAT)和谷胱甘肽S转移酶(GST)水平显著升高。在右美托咪定治疗组中,TBARS、NOS、CAT和GST水平显著低于D-I/R组。在组织病理学评估中,与对照组相比,DM-I/R组的肾小球空泡化(GV)、肾小管扩张(TD)、血管空泡化和肥大(VVH)、肾小管细胞变性和坏死(TCDN)、肾小管透明管型(THC)、白细胞浸润(LI)和肾小管细胞溢出(TCS)显著增加。此外,与DM-I/R组相比,右美托咪定治疗组(DM-I/R-D组)的GV、VVH和THC水平显著降低。
我们发现,糖尿病大鼠在缺血前30分钟腹腔注射100μg/kg右美托咪定可改善脂质过氧化、氧化应激和缺血/再灌注相关的肾损伤。我们认为,糖尿病大鼠在缺血/再灌注前给予右美托咪定具有肾脏保护作用。