Iskandarov Emil, Kadaba Srinivasan Pramod, Xin Wang, Bleilevens Christian, Afify Mamdouh, Hamza Astrit, Wei Lai, Hata Koichiro, Agayev Boyukkishi, Tolba Rene
Department of Hepato-biliary and Pancreas Surgery, Scientific Center of Surgery named after academician M.A.Topchubashov, Baku, Azerbaijan.
Institute for Laboratory Animal Science and Experimental Surgery, University Hospital, RWTH Aachen University, Aachen, Germany.
Hepat Mon. 2016 Jul 24;16(8):e36821. doi: 10.5812/hepatmon.36821. eCollection 2016 Aug.
To investigate the role of CGS21680, a selective adenosine A2A receptor agonist, on a bile-duct-ligated cirrhotic liver resection model in rats.
Male Wistar rats were allotted into 3 groups (n = 7 per time-point): the control group, the bile duct ligation + CGS21680 group (BDL + CGS), and the bile duct ligation group (BDL). Biliary cirrhosis had been previously induced by ligature of the common bile duct in the BDL + CGS and BDL groups. After 2 weeks, the animals underwent partial hepatectomy (50%). The BDL + CGS group received a single dose of CGS21680 15 minutes prior to hepatectomy. Blood samples were collected and analyzed.
Aspartate transaminase levels were found to be lower in the control vs BDL groups (1, 3, and 24 h) (P < 0.01) and the BDL + CGS (1 and 3 hours) (P < 0.01) and BDL + CGS vs BDL (24 hours) (P < 0.05) groups. Hepatic flow was measured and BDL showed significantly lower values at the 3, 24, and 168 h time-points compared to the control (P < 0.01) and BDL + CGS groups (P < 0.05 at 3 and 168 hours; P < 0.01 at 24 h). O2C velocity was reduced in the BDL compared to the control group (P < 0.001 at 3 hours; P < 0.01 at 24 and 168 hours) and the BDL + CGS group (P < 0.01 at 24 hours). Interleukin-6 levels were abrogated in the BDL + CGS (P < 0.05) and control (P < 0.01) groups versus BDL. Histone-bound low-molecular-weight DNA fragments in the BDL + CGS (P < 0.01) and control (P < 0.05) groups were low compared to the BDL group.
Administration of CGS21680, an adenosine receptor agonist, after the resection of bile-duct-ligated cirrhotic livers led to improved liver function, regeneration, and microcirculation.
研究选择性腺苷A2A受体激动剂CGS21680在大鼠胆管结扎性肝硬化肝切除模型中的作用。
将雄性Wistar大鼠分为3组（每个时间点n = 7）：对照组、胆管结扎+CGS21680组（BDL + CGS）和胆管结扎组（BDL）。BDL + CGS组和BDL组先前已通过结扎胆总管诱导了胆汁性肝硬化。2周后，动物接受部分肝切除术（50%）。BDL + CGS组在肝切除术前15分钟接受单剂量的CGS21680。采集血样并进行分析。
发现对照组与BDL组（1、3和24小时）以及BDL + CGS组（1和3小时）相比，天冬氨酸转氨酶水平较低（P < 0.01），且BDL + CGS组与BDL组（24小时）相比（P < 0.05）。测量肝血流量，与对照组（P < 0.01）和BDL + CGS组（3和168小时时P < 0.05；24小时时P < 0.01）相比，BDL组在3、24和168小时时间点的值显著较低。与对照组（3小时时P < 0.001；24和168小时时P < 0.01）和BDL + CGS组（24小时时P < 0.01）相比，BDL组的氧摄取率降低。与BDL组相比，BDL + CGS组（P < 0.05）和对照组（P < 0.01）的白细胞介素-6水平降低。与BDL组相比，BDL + CGS组（P < 0.01）和对照组（P < 0.05）中组蛋白结合的低分子量DNA片段较少。
在胆管结扎性肝硬化肝脏切除术后给予腺苷受体激动剂CGS21680可改善肝功能、肝脏再生和微循环。
