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Phycocyanobilin accelerates liver regeneration and reduces mortality rate in carbon tetrachloride-induced liver injury mice

机译:藻蓝素可促进四氯化碳诱导的肝损伤小鼠的肝脏再生并降低死亡率

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摘要

AIM: To investigate the hepatoprotective effects of phycocyanobilin (PCB) in reducing hepatic injury and accelerating hepatocyte proliferation following carbon tetrachloride (CCl4) treatment.METHODS: C57BL/6 mice were orally administered PCB 100 mg/kg for 4 d after CCl4 injection, and then the serum and liver tissue of the mice were collected at days 1, 2, 3, 5 and 7 after CCl4 treatment. A series of evaluations were performed to identify the curative effects on liver injury and recovery. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and superoxide dismutase (SOD) were detected to indirectly assess the anti-inflammatory effects of PCB. Meanwhile, we detected the expressions of hepatocyte growth factor, transforming growth factor alpha (TGF-α), TGF-β, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), the factors which are associated with inflammation and liver regeneration. The protein expressions of proliferating cell nuclear antigen (PCNA), TNF-α and cytochrome C were detected by western blot. Furthermore, the survival rates were analyzed of mice which were administered a lethal dose of CCl4 (2.6 mg/kg) with or without PCB.RESULTS: In our research, PCB showed a strongly anti-inflammatory effect on CCl4-induced liver injury in mice. The ALT was significantly decreased after CCl4 treatment from day 1 (P < 0.01) and the AST was significantly decreased from day 2 (P < 0.001). Both albumin and liver SOD were increased from day 2 (P < 0.001 and P < 0.01), but serum SOD levels did not show a significant increase (P > 0.05). PCB protected the structure of liver from the injury by CCl4. TUNEL assay showed that PCB dramatically reduced the number of apoptotic cells after CCl4 treatment compared to the control (101.0 ± 25.4 vs 25.7 ± 6.4, P < 0.01). The result of western blotting showed that PCB could increase PCNA expression, decrease TNF-α and cytochrome C expression. Furthermore, data shows that PCB could improve the survival rate of acute liver failure (ALF) mice which were injected with a lethal dose of CCl4 (60.0% vs 20.0%).CONCLUSION: Our study indicated that PCB could be an ideal candidate for reversing acute liver injury or ALF.
机译:目的:研究四氯化碳(CCl4)处理后藻蓝蛋白(PCB)对减轻肝脏损伤和促进肝细胞增殖的保肝作用。方法:C57BL / 6小鼠在注射CCl4后4 d口服PCB 100 mg / kg,并且然后在CCl4处理后第1、2、3、5和7天收集小鼠的血清和肝组织。进行了一系列评估,以确定对肝损伤和恢复的疗效。检测天冬氨酸转氨酶(AST),丙氨酸转氨酶(ALT),白蛋白和超氧化物歧化酶(SOD)间接评估PCB的抗炎作用。同时,我们检测了肝细胞生长因子,转化生长因子α(TGF-α),TGF-β,肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的表达,这些因子与伴随炎症和肝脏再生。 Western blot检测增殖细胞核抗原(PCNA),TNF-α和细胞色素C的蛋白表达。此外,分析了使用致命剂量的CCl4(2.6 mg / kg)或不使用PCB的小鼠的存活率。结果:在我们的研究中,PCB显示出对CCl4诱导的小鼠肝损伤的强抗炎作用。从第1天开始,CCl4处理后ALT显着降低(P <0.01),从第2天起AST显着降低(P <0.001)。从第2天开始,白蛋白和肝脏的SOD均升高(P <0.001和P <0.01),但血清SOD含量却没有显着升高(P> 0.05)。 PCB保护肝脏结构不受CCl4伤害。 TUNEL分析显示,与对照组相比,PCB板在CCl4处理后显着减少了凋亡细胞的数量(101.0±25.4 vs 25.7±6.4,P <0.01)。 Western blotting结果表明,PCB可以增加PCNA的表达,降低TNF-α和细胞色素C的表达。此外,数据显示PCB可以提高注射致命剂量CCl4的急性肝衰竭(ALF)小鼠的存活率(60.0%对20.0%)。结论:我们的研究表明PCB可以逆转的理想候选药物。急性肝损伤或ALF。

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