Decreased Plasma Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Levels are Linked with Disease Severity in Patients with Liver Cirrhosis

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide that has been found to reduce liver inflammation and protect liver from steatosis. We aimed to measure the level of plasma PACAP in patients with liver cirrhosis and to correlate its level with disease severity and laboratory parameters. 113 patients with clinically diagnosed liver cirrhosis and 110 healthy individuals were selected. Child–Pugh score was performed to evaluate disease severity. Liver biopsy was performed using the Knodell modified histology activity index (KmHAI). The L3 skeletal muscle index (L3SMI) was calculated to evaluate the nutrition status. Plasma PACAP concentrations were detected using ELISA. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the sensitivity and specificity of PACAP for detecting the severity of liver cirrhosis. Plasma PACAP levels were found to be significantly downregulated in patients with liver cirrhosis compared with healthy controls. The case group included 38 Child–Pugh A patients, 39 Child–Pugh B patients, and 36 Child–Pugh C patients. Cirrhosis patients with Child–Pugh C had significantly lower plasma PACAP levels compared with those with Child–Pugh B and A. Cirrhosis patients with Child–Pugh B demonstrated markedly decreased plasma PACAP concentrations compared with those with Child–Pugh A. ROC curve analysis indicated that low level of plasma PACAP may act as a potential indicator for disease progression of liver cirrhosis determined by Child–Pugh classification at both compensation stage (Child–Pugh A developed to Child–Pugh B) and decompensation stage (Child–Pugh B developed to Child–Pugh C).In addition, plasma PACAP levels were inversely associated with KmHAI and ALT as well as AST levels. In both male and female patients, plasma PACAP levels were positively related to L3SMI score. Decreased plasma PACAP levels are linked with disease severity in patients with liver cirrhosis. Reduced plasma PACAP may serve as a biomarker for detection and assessment of the severity of liver cirrhosis.

     

凋亡诱导因子的研究进展

凋亡诱导因子(apoptosis-inducing factor,AIF)是一类存在于线粒体内外膜间隙的保守的黄素蛋白,具有双重功能。在细胞正常的生理状态下,作为线粒体氧化还原酶,能催化细胞色素c(Cytc)和NAD之间的电子传递,当细胞受到凋亡刺激后,就从膜间隙释放到细胞质中,并通过其核定位信号序列(nuclear localization sequence,NLS)进入细胞核内,引起染色体核周边凝集和DNA呈大片段断裂(约50kb),进而引发不依赖于caspase的细胞凋亡。AIF的释放受Bcl-2家族蛋白的调控,同时也受Hsp70的抑制,它还是多聚(ADP核糖)聚合酶1[poly(ADP-ribose)polymerase1,PARP1]介导的细胞凋亡途径的下游效应物。