| Acute lung injury (ALI) is a common devastating symptom, which has been thought to be a tough problem in critical medicine for its high morbidity and mortality. Electroacupuncture is based on the traditional acupuncture, but it can achieve better treatment effect.Clinical and animal studies have confirmed that acupuncture can enhance the body’s immune function, improve microcirculation and energy metabolism disorders.Our previous study have demonstrated that electroacupuncture can reduce lipopolysaccharide (LPS) induced lung damage degree by upregulating the heme oxygenase1(HO-1) expression, but the specific mechanism remain unclear. PKCa is the most prominent member of PKC family. Through the activation of PKCa and subsequent HO-1up-regulation, radix scutellariae could exert its cell protection role. P38is a member of the MAPK family, its activation is required in the process of heme oxygenase-1expression regulated by toll-like receptor4after hemorrhagic shock induced acute lung injury in mice. However, there is no literature report that demonstrates whether PKCa and p38MAPK pathway participates in electro-acupuncture mediated HO-1expression during endotoxic shock induced acute lung injury in rabbits.Objective To evaluate the effect of PKCa and p38MAPK pathway in the up-regulation of HO-1expression regulated by electro-acupuncture during endotoxic shock-induced ALI in rabbits.Methods140healthy male New Zealand white rabbits is randomly divided into two parts,each part contains7groups(n=10each).Part1:sham operation group (group S); alcohol group(AL);PKC inhibitor chelerythrine group (CHE); LPS group (L); EA+LPS group (EA); Non EA+LPS group (NEA); EA+LPS+chelerythrine group (EAC).Part2:sham opration group (S),Alcohol group (AL),SB203580group (SB), endotoxic shock-induced acute lung injury model group (M), EA+endotoxic shock-induced acute lung injury model group (EAM),sham EA+endotoxic shock-induced acute lung injury model group (SEAM),EA+endotoxic shock-induced acute lung injury model+SB203580group (EAMS). LPS5mg/kg in2ml normal saline was injected intravenously in groups L, EA,NEA, EAC, M,EAM,SEAM and EAMS,while the same volume normal saline was injected in group S, AL, CHE and group SB. Endotoxin shock-induced ALI was confirmed by MAP decrease to75%of baseline value and PaO2/FiO2≤300.8mg/kg chelerythrine was injected intraperitoneally in groups CHE, EAC and SB2035805μmol/kg was injected intravenously in groups S, EAMS0.5h before LPS administration, while0.5ml normal saline was injected in group S, and same volume alcohol was injected in other groups in the same way. Bilateral EA stimulation of ST36and BL13were performed for a four-consecutive-day. Disperse-dense waves of alternating frequencies of2and15Hz were applied at an intensity of1-2mA for30min every day. EA stimulation was also performed throughout the experiment procedure for6h at the experimental day. To control the effects of electrical and needle stimulation, sham electroacupuncture group was acupunctured at non-acupoints which are located0.5cm obliquely superior and lateral to ST36or BL13acupoint with the same frequency and intensity. Blood samples were taken from right common carotid artery for measurement of serum TNF-a at6h after LPS administration.Then the rabbits were sacrificed by blood-letting, the lungs were removed for microscopic examination and pathological injury score. W/D ratio, MDA content, SOD activity, and expression of HO-1, PKCα,p38MAPK protein and p-p38MAPK protein.Results LPS-induced endotoxic shock significantly increased lung injury level and HO-1expression, however these injury conditions induced by LPS could be alleviated through further increase of HO-1regulated by EA, but it can be counteracted in some degree when infused p38MAPK inhibitor SB203580and PKCa inhibitor chelerythrine.Conclusion PKC a and p38MAPK activation is involved in the up-regulation of HO-1expression regulated by electro-acupuncture during endotoxic shock-induced ALI in rabbits. |
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