Zhuonan Zhuang1, Peilong Lian2, Xiaojuan Wu3, Baoxu Shi4, Maoyou Zhuang5, Ruiling Zhou6, Rui Zhao2, Zhen Zhao2, Sen Guo2, Zhipeng Ji7, Kesen Xu2. 1. Department of General Surgery, Beijing Tsinghua Changgung Hospital Medical Center, Tsinghua University Beijing 102218, China. 2. Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University Jinan 250012, China. 3. Department of Nephrology, Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second Hospital Huai'an 223002, P.R. China. 4. Department of Neurology, People's Hospital of Rizhaolanshan Rizhao 276800, China. 5. Department of Neurology, Rizhao First People Hospital Rizhao 276800, China. 6. Department of Clinical Lab, Rizhao First People Hospital Rizhao 276800, China. 7. Department of General Surgery, The Second Affiliated Hospital of Shandong University Jinan 250033, China.
Abstract
OBJECTIVE: Aim of this study is to protect donor liver against ischemia-reperfusion injury by abating Cytochrome C induced apoptosome on rat model. METHODS: A total of 25 clean SD inbred male rats were used in this research. The rats in ischemia-reperfusion injury group (I/R group, n=5) were under liver transplantation operation; rats in dichloroacetate diisopropylamine group (DADA group, n=5) were treated DADA before liver transplantation; control group (Ctrl group, n=5); other 10 rats were used to offer donor livers. RESULTS: In DADA therapy group, Cytochrome C expression in donor hepatocellular cytoplasm was detected lower than that in I/R group. And the Cytochrome C induced apoptosome was also decreased in according to the lower expressions of Apaf-1 and Caspase3. Low level of cleaved PARP expression revealed less apoptosis in liver tissue. The morphology of donor liver mitochondria in DADA group was observed to be slightly edema but less than I/R group after operation 12 h. The liver function indexes of ALT and AST in serum were tested, and the results in DADA group showed it is significantly lower than I/R group after operation 12 h. The inflammation indexes of IL-6 and TNF-α expressions in DADA group were significantly lower than that in I/R group after operation 24 h. CONCLUSION: The dichloroacetate diisopropylamine treatment could protect the hepatocellular mitochondria in case of the spillage of Cytochrome C induced apoptosome, and protect the liver against ischemia-reperfusion injury. Thus, it may be a method to promote the recovery of donor liver function after transplantation.
OBJECTIVE: Aim of this study is to protect donor liver against ischemia-reperfusion injury by abating Cytochrome C induced apoptosome on rat model. METHODS: A total of 25 clean SD inbred male rats were used in this research. The rats in ischemia-reperfusion injury group (I/R group, n=5) were under liver transplantation operation; rats in dichloroacetate diisopropylamine group (DADA group, n=5) were treated DADA before liver transplantation; control group (Ctrl group, n=5); other 10 rats were used to offer donor livers. RESULTS: In DADA therapy group, Cytochrome C expression in donor hepatocellular cytoplasm was detected lower than that in I/R group. And the Cytochrome C induced apoptosome was also decreased in according to the lower expressions of Apaf-1 and Caspase3. Low level of cleaved PARP expression revealed less apoptosis in liver tissue. The morphology of donor liver mitochondria in DADA group was observed to be slightly edema but less than I/R group after operation 12 h. The liver function indexes of ALT and AST in serum were tested, and the results in DADA group showed it is significantly lower than I/R group after operation 12 h. The inflammation indexes of IL-6 and TNF-α expressions in DADA group were significantly lower than that in I/R group after operation 24 h. CONCLUSION: The dichloroacetate diisopropylamine treatment could protect the hepatocellular mitochondria in case of the spillage of Cytochrome C induced apoptosome, and protect the liver against ischemia-reperfusion injury. Thus, it may be a method to promote the recovery of donor liver function after transplantation.
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