Effects Of Human Urinary Kallidinogenase On Expression Of CGRP, RAMP1 And VEGF In Rats Suffered Focal Cerebral Ischemia

BackgroundIschemic stroke attaches a great importance of all aspects because of its high incidence, high case fatality rate, high morbidity and increasingly younger characteristics. Venous or arterial thrombolysis therapy can early dredge infarction and greatly alleviate the damage caused by it. However, due to the limitation of medical condition and therapeutic time window, thrombolysis therapy is hampered by a lot. After the occurrence of cerebral infarction, angiogenesis increases around infarcts and the increasing new blood vessels can effectively promote repairing of nerves in damaged brain tissues. Currently, no matter in clinical or in experiment, the study of angiogenesis after cerebral infarction has become a new direction for the treatment of ischemic crebral. Human urinary kallidinogenase can cut low molecular weight peptide and release vasoactive peptide- activated peptides. Activated peptides incorporation with high affinity B1/B2 receptor, could promote angiogenesis after infarction and get good curative effect in treatment of ischemic cerebral. CGRP(calcitonin gene related peptide) is an important capsaicin sensitive sensory nerve peptide neurotransmitter contained 37 amino acid residues widely distributed central and peripheral nervous system. CGRP has the role of significantly promoting angiogenesis. Besides, it increases local blood flow and stimulates new angiogenesis to make the ischemic tissue alive. RAMP1(receptor activity modifying protein 1) is thekey receptor subunits of CGRP, determined CGRP’sreceptor activity and biological function. This experiment trying to study the correlation of new blood vessels with CGRP、RAMP1 after ischemia and the influence of human urinary kallidinogenase on the expression of them in the brain tissue to understand the condition of CGRP、RAMP1 expressed in the ischemic brain tissue, the correlation between angiogenesis and CGRP、RAMP1and the influence of human urinary kallidinogenase on the expression of them in the brain tissue.Objective To study the effect of human urinary kallidinogenase on expression of CGRP、RAMP1 and VEGF in rats suffered focal cerebral ischemia. Methods 80 male SD rats were randomly divided into four groups: sham operation group(S group), ischemia group(I group), low dose of kallidinogenase(3.75×10-3 PNA /(kg·d), I + Kall group) and high dose of kallidinogenase(17.25×10-3PNA/(kg·d), I + Kal2 group). Each group has 20 rats. Using line bolt blocks the right middle cerebral artery in rats to establish the right MCAO ischemia model after tail intravenous dosing 1 week. TTC method was used to measure the cerebral infarction volume. Immunohistochemistry and Western blot were used to evaluate the expression of CGRP protein in the hippocampus and the expression of RAMP1 and VEGF protein in the cerebral cortex. Results Compared with the S group, the expression of CGRP、RAMP1 and VEGF increase significantly in I group rat(P<0.01). While, compared with I group, kallidinogenase high and low dose group can significantly reduce cerebral infarction and markedly increase the expression of CGRP、RAMP1 and VEGF induced in cerebral ischemia 24 h after MCAO(P<0.05). Conclusion Human urinary kallidinogenase can promote the expression of CGRP and RAMP1 in ischemic brain tissues andthis may be one of the mechanisms of promoting angiogenesis after cerebral...