Calcitonin Gene-Related Peptide Downregulates Expression of Inducible Nitride Oxide Synthase and Caspase-3 after Intestinal Ischemia-Reperfusion Injury in Rats.
Various investigations have demonstrated that calcitonin gene-related peptide (CGRP) plays an important role in mediating ischemic preconditioning. CGRP has been shown to mimic the protective effects of ischemic preconditioning and mitigate ischemia-reperfusion (I/R) injury in the heart, brain, gastrointestinal system, and other tissues. This study aimed to examine whether CGRP, a proven intestinal cytoprotective molecule, exerted its protective effects through modulation of inducible nitride oxide synthase (iNOS) and apoptosis after intestinal I/R injury.



This animal study randomly divided 30 rats into the following five groups: (1) the normal control group, (2) the ischemia group with normal saline, (3) the I/R group with normal saline, (4) the ischemia group with CGRP (300 μg/kg), and (5) the I/R group with CGRP (300 μg/kg). Levels of iNOS messenger RNA (mRNA) and protein, and caspase-3 protein were determined by real-time quantitative polymerase chain reaction and Western blotting analyses, respectively. Statistical analysis was performed using analysis of variance with Dunn test.



The mRNA levels of iNOS increased after the intestinal ischemia or intestinal reperfusion phase (p < 0.01), and CGRP pretreatment significantly decreased iNOS mRNAs and protein levels (p < 0.01). The expression protein levels of caspase-3 increased after the intestinal ischemia or intestinal reperfusion phase. CGRP pretreatment significantly decreased the levels of caspase-3 proteins. CGRP intestinal cytoprotection is mediated, in part, by downregulation of expression of iNOS and caspase-3 after intestinal I/R injury.



The study indicates that the cytoprotective role of CGRP (i.e., antiapoptotic effect) after I/R injury could be via downregulation of iNOS, which may relieve I/R tissue damage by blocking iNOS activity.
Division of Pediatric Surgery, Department of Surgery, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan.
Chih-Cheng
CC
Luo
Division of Pediatric Surgery, Department of Surgery, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan.
Chen-Sheng
CS
Huang
Department of Pediatric Surgery, Chang Gung Children's Medical Center, Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan.
Yung-Ching
YC
Ming
Division of Neonatology, Chang Gung Children's Medical Center, Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan.
Shih-Ming
SM
Chu
Division of Pediatric Gastroenterology, Chang Gung Children's Medical Center, Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan. Electronic address: chaohero@yahoo.com.
Hsun-Chin
HC
Chao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism*; D004195:Disease Models, Animal; D007410:Intestinal Diseases / Q000209:etiology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3; D015740:Calcitonin Gene-Related Peptide
calcitonin gene-related peptide; caspase-3; inducible nitride oxide synthase; ischemia-reperfusion injury; small intestine