Cholecystokinin protects mouse liver against ischemia and reperfusion injury
INTERNATIONAL IMMUNOPHARMACOLOGY
Authors: Zhang, Ying; Zhu, Jiali; Guo, Long; Zou, Yun; Wang, Fang; Shao, Han; Li, Jinbao; Deng, Xiaoming
Abstract
Background: Cholecystokinin (CCK), as a gastrointestinal hormone, has an important protective role against sepsis or LPS-induced endotoxic shock. We aim to address the role of CCK in hepatic ischemia followed by reperfusion (I/R) injury. Materials and methods: A murine model of 60 min partial hepatic ischemia followed by 6 h of reperfusion was used in this study. CCK and CCKAR Levels in blood and liver were detected at 3 h, 6 h, 12 h and 24 h after reperfusion. Then the mice were treated with CCK or proglumide, a nonspecific CCK-receptor (CCK-R) antagonist. Mice were randomly divided into four groups as follows: (1) sham group, in which mice underwent sham operation and received saline; (2) I/R group, in which mice were subjected to hepatic I/R and received saline; (3) CCK group, in which mice were subjected to hepatic I/R and treated with CCK (400 mu g/kg); (4) proglumide group (Pro), in which mice underwent hepatic I/R and treated with proglumide (3 mg/kg); CCK and proglumide were administrated via tail vein at the moment of reperfusion. Serum AST (BAST) and serum ALT (sALT) were determined with a biochemical assay and histological analysis were performed with hematoxylin-eosin (H&E). Cytokines (IL-1 beta, IL-6, IL-10, TNE-alpha) expressions in blood were determined with enzyme-linked immunosorbent assay (ELISA). The MPO (myeloperoxidase) assay were used to measure neutrophils' infiltration into the liver. The apoptotic index (TUNEL-positive cell number/total liver cell number x 100%) was calculated to assess hepatocelluar apoptosis. Finally, activation of NF-kappa B and phosphor-p38 expression in liver homogenates were analyzed with Western Blot (WB). Results: Our findings showed that 1) CCK and CCK-AR were upregulated in our experimental model over time; 2) Treatment with CCK decreased sAST/SALT levels, inflammatory hepatic injury, neutrophil influx and hepatocelluar apoptosis, while proglumide aggravated hepatic injury. Conclusion: These findings support our hypothesis and suggest that CCK played a positive role in the ongoing inflammatory process leading to liver I/R injury. (C) 2017 Published by Elsevier B.V.
Association of GA genotype of SNP rs4680 in COMT gene with psoriasis
ARCHIVES OF DERMATOLOGICAL RESEARCH
Authors: Sobolev, Vladimir; Sakaniya, Luiza; Tretiakov, Artemii; Kokaeva, Zarema; Naumova, Elena; Rudko, Olga; Soboleva, Anna; Danilin, Ivan; Korsunskaya, Irina; Klimov, Eugene
Abstract
Psoriasis is a multigene and multifactorial skin disease with heterogeneous genetic inheritance. Mental disorders participate in the development of psoriasis as predisposing factors; a correlation of dermatological diseases with pathological anxiety and stress was shown. Meanwhile, there are no studies describing molecular mechanisms of the linkages between psycho-emotional disorders and skin diseases. The aim of this study is to find the associations between SNP in genes COMT (rs4680), DBH (rs141116007), CCKAR (rs1800857) and CCKBR (rs1805002), and psoriasis. Patients were selected according to the 10th revision of International Classification of Diseases (L-40). The sample size was 88 patients. The size of the control sample (population control) was 365 people. Genotyping was performed using PCR-RFLP and real-time PCR. Statistical analysis was performed using WinPepi software. Identification of complex genotypes was performed by the Monte Carlo method using APSampler 3.6.1 algorithm. Among the studied genes, only GA genotype of COMT gene is significantly associated with psoriasis [chi(2) = 19.163 (p = 1.3E-5), F (p) = 1.2E-5, OR 3.47 (CI 99% = 1.61-7.91)]. At the moment, the functional significance of this phenomenon is difficult to explain.