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尿石素A预处理对肝缺血再灌注损伤大鼠模型的保护作用
Protective effect of urolithin A pretreatment in a rat model of hepatic ischemia-reperfusion injury
文章发布日期:2020年07月09日  来源:  作者:米凯,黄锐  点击次数:603次  下载次数:44次

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【摘要】:目的 探讨尿石素A(Uro-A)对肝缺血再灌注损伤(HIRI)大鼠模型的保护作用。方法 将40只SD大鼠随机分为假手术组、模型组、Uro-A低剂量组(1 mg/kg)和Uro-A高剂量组(3 mg/kg),每组10只。造模前Uro-A低剂量和高剂量组每天灌胃药物1次,持续5 d。动物麻醉后造模,恢复血流后6 h检测血清中ALT、AST与乳酸脱氢酶(LDH)的含量,ELISA法检测肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、IL-1β、IL-6和TNFα含量,观察肝脏病理损伤与肝细胞凋亡情况,Western Blot法检测肝脏中内质网分子伴侣葡萄糖调节蛋白78(GRP78)、下游应激转录因子(CHOP)和凋亡蛋白家族(Caspase-12)的表达水平。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果 Uro-A高剂量组ALT、AST、LDH、MDA、CAT、IL-1β、IL-6、TNFα、CHOP、GRP78、Caspase-12水平及凋亡率均较模型组降低,SOD含量较模型组升高,差异均有统计学意义(P值均<0.05)。模型组肝脏结构破坏严重,阳性率90%,Uro-A高剂量组肝脏结构完好,未见明显组织增生与炎性细胞增多,阴性率80%。与Uro-A高剂量组相比,Uro-A低剂量组ALT、AST、LDH水平和细胞凋亡率均显著升高(P值均<0.05)。结论 Uro-A预处理可降低大鼠肝脏缺血再灌注造成的损伤,减少氧化损伤与炎症因子的释放,其机制与通过抑制内质网应激通路减少肝细胞的凋亡有关。
【Abstract】:Objective To investigate the protective effect of urolithin A (Uro-A) against hepatic ischemia-reperfusion injury (HIRI) in rats. Methods A total of 40 Sprague-Dawley rats were randomly divided into sham-operation group, model group, low-dose Uro-A (1 mg/kg) group, and high-dose Uro-A (3 mg/kg) group, with 10 rats in each group. Before modeling, the rats in the low- and high-dose Uro-A groups were given the drug by gavage once a day for 5 consecutive days. The model was established after anesthesia, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured at 6 hours after the recovery of blood flow. ELISA was used to measure the content of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the liver, and liver pathological injury and hepatocyte apoptosis were evaluated. Western blot was used to measure the expression of the endoplasmic reticulum chaperone glucose-regulated protein 78 (GRP78), the downstream transcription factor CHOP, and the apoptosis protein caspase-12 in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the model group, the high-dose Uro-A group had significantly lower levels of ALT, AST, LDH, MDA, CAT, IL-1β, IL-6, TNF-α, CHOP, GRP78, and caspase-12 and apoptosis rate and a significantly higher content of SOD (all P<0.05). The model group had severe damage of liver structure, with a positive rate of 90%, while the high-dose Uro-A group had intact liver structure without obvious tissue proliferation or inflammatory cell proliferation, with a negative rate of 80%. Compared with the high-dose Uro-A group, the low-dose Uro-A group had significant increases in the levels of ALT, AST, and LDH and apoptosis rate (all P<0.05). Conclusion Uro-A pretreatment can alleviate liver ischemia-reperfusion injury in rats and reduce oxidative damage and the release of inflammatory factors, possibly by inhibiting the endoplasmic reticulum stress pathways and reducing hepatocyte apoptosis.
【关键字】:肝疾病; 再灌注损伤; 尿石素A; 大鼠,Sprague-Dawley
【Key words】:liver diseases; reperfusion injury; urolithin A; rats,Sprague-Dawley
【引证本文】:MI K, HUANG R. Protective effect of urolithin A pretreatment in a rat model of hepatic ischemia-reperfusion injury[J]. J Clin Hepatol, 2020, 36(8): 1783-1787. (in Chinese)
米凯, 黄锐. 尿石素A预处理对肝缺血再灌注损伤大鼠模型的保护作用[J]. 临床肝胆病杂志, 2020, 36(8): 1783-1787.

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