Cobra Venom Factor-induced complement depletion protects against lung ischemia reperfusion injury through alleviating blood-air barrier damage

Chang Haihua,Liao Yuanli,Lin Fei,Wang Wei,Huang Kun

doi:10.1038/s41598-018-28724-z

Abstract

The purpose of this study was to study whether complement depletion induced by pretreatment with Cobra Venom Factor (CVF) could protect against lung ischemia reperfusion injury (LIRI) in a rat model and explore its molecular mechanisms. Adult Sprague-Dawley rats were randomly assigned to five groups (n = 6): Control group, Sham-operated group, I/R group, CVF group, I/R + CVF group. CVF (50 μg/kg) was injected through the tail vein 24 h before anesthesia. Lung ischemia reperfusion (I/R) was induced by clamping the left hilus pulmonis for 60 minutes followed by 4 hours of reperfusion. Measurement of complement activity, pathohistological lung injury score, inflammatory mediators, pulmonary permeability, pulmonary edema, integrity of tight junction and blood-air barrier were performed. The results showed that pretreatment with CVF significantly reduced complement activity in plasma and BALF. Evaluation in histomorphology showed that complement depletion induced by CVF significantly alleviated the damage of lung tissues and inhibited inflammatory response in lung tissues and BALF. Furthermore, CVF pretreatment had the function of ameliorating pulmonary permeability and preserving integrity of tight junctions in IR condition. In conclusion, our results indicated that complement depletion induced by CVF could inhibit I/R-induced inflammatory response and alleviate lung I/R injury. The mechanisms of its protective effects might be ameliorated blood-air barrier damage.

Highlights

Ischemia-reperfusion (I/R) injury is a serious clinical event which can take place in diverse conditions, such as organ transplantation, shock, cardiac arrest, thoracic surgery and multiple trauma[1,2]
The results demonstrated that Cobra Venom Factor (CVF) significantly reduced complement activity and could induce complement depletion in a rat model (P < 0.05)
In ischemia reperfusion (I/R) + CVF group, lung tissue structures were roughly intact, a small number of red blood cells and neutrophils had infiltrated into the alveolar space

Summary

Introduction

Ischemia-reperfusion (I/R) injury is a serious clinical event which can take place in diverse conditions, such as organ transplantation, shock, cardiac arrest, thoracic surgery and multiple trauma[1,2]. The uncontrollable complement activation is considered to be responsible for the pathogenesis mechanism of acute lung injury (ALI) induced by I/R. Cobra Venom Factor (CVF) is a non-toxic protein purified from cobra venom It is a structural analogue of complement component C3 and has the function of complement activation[13]. Several studies have shown that complement depletion caused by treatment of CVF plays a beneficial effect in the pathological process of transplantation[15,16,17]. This study aimed to clarify the role of complement depletion induced by CVF in blood-air barrier during LIRI development. This novel mechanism provides a potential role for complement depletion in LIRI therapeutic applications

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Conclusion