The Clinical And Basic Research Of Prone Ventilation In The Treatment Of ARDS Caused By Sepsis

Objective: Acute respiratory distress syndrome caused by sepsis has become a clinical syndrome that seriously threatens the life of severe patients.It is imperative to get effective treatment.This study intends to study the clinical efficacy of prone ventilation in the treatment of ARDS caused by sepsis and explore its possible mechanism through clinical retrospective analysis and animal experiments.Methods:Two parts were included in the study.In the first part,patients(n=102)with ARDS were divided into the routine(n=55)and PPV treatment groups(n=47).The oxygenation index,lung compliance(Cst)and platform pressure(Pplat)were compared after ventilation in each group.The heart rate(HR),mean arterial pressure(MAP),central venous pressure(CVP),left ventricular ejection fraction(LVEF),the length of mechanical ventilation time and ICU stay,and levels of C-reactive protein(CRP),procalcitonin(PCT),and interleukin-6(IL-6)after ventilation,the 28 day and90 day mortality of the two groups were compared.In the second part,taking cecal ligation and perforation leading to Escherichia coli peritonitis and septic ARDS rats as the model,this paper discusses the molecular pathogenesis of ARDS and the effect of prone position on RIPK3 signal pathway,in order to put forward a possible new way for the prevention and treatment of septic ARDS.A rat model of ARDS caused by sepsis was established.The supine position was maintained for 3 hours in the sham operation group;The operation group was given placebo or RIPK3 inhibitor 30 minutes before modeling;The supine position was maintained for 3h after modeling in the operation + supine position group,and the prone position was maintained for3 h after modeling in the operation + prone position group.Three hours after modeling,blood was collected from inferior vena cava,and the supernatant was taken for preservation after low-temperature centrifugation.After taking blood,take lung tissue for standby.The wet dry ratio of the left lung was measured,and the pathological conditions were observed by HE staining after partial right lung fixation.The expression of RIPK3 protein was detected by immunohistochemistry.The expression of RIPK3 protein was detected by WB in some right lung tissues.Results: In the first part,on the first day after ventilation,the oxygenation index and Cst were higher and Pplat level was lower in the PPV group than the conventional treatment group(P <0.05).There was no significant difference in oxygenation index,Cst,and Pplat levels between the two groups on the 2nd,4th,and7 th day after ventilation(P >0.05).There were no significant differences in HR,MAP,CVP,LVEF,duration of mechanical ventilation and ICU stay,and the levels of CRP,PCT,and IL-6 between the two groups on the first day after ventilation(all P >0.05).The mortality rates on days 28 and 90 in the PPV and conventional treatment groups were 12.77% and 29.09%,and 25.53% and 45.45%,respectively(P <0.05).In the second part,the dry wet ratio of left lung in each group was detected 3 hours after modeling.Compared with the placebo supine group,the dry wet ratio in the inhibitor prone group increased,and there was a big difference(P < 0.05);The pathological conditions of each group were examined.The microscopic observation of he stained sections of rats showed that the lung structure of rats in the sham operation group was clear;In the operation + supine position placebo group and operation + prone position placebo group,the normal structure of lung tissue was destroyed,alveolar epithelium was diffusely damaged,and pulmonary interstitial hemorrhage was accompanied by a large number of inflammatory cell infiltration;The lung structure of rats in operation+ supine RIPK3 inhibitor group was clear,but there was still some diffuse injury of alveolar epithelium,while the lung structure of rats in operation + supine RIPK3 inhibitor group was clear,suggesting that RIPK3 inhibitor has a certain therapeutic effect on ARDS model rats,and the therapeutic effect of prone position is better than that of supine position;The expression of RIPK3 protein in each group was detected by immunohistochemistry and WB.The results of immunohistochemistry and WB showed that the expression level of RIPK3 protein in operation + supine placebo group and operation + prone placebo group was much higher than the control part(P< 0.05).Compared with the operation + supine position placebo group,the expression level of RIPK3 protein in the operation + supine position RIPK3 inhibitor group decreased significantly.Compared with the operation + prone position placebo group,the expression level of RIPK3 protein in the operation + prone position RIPK3 inhibitor group decreased significantly(P < 0.05),suggesting that RIPK3 inhibitor can effectively reduce the expression level of RIPK3 in ARDS model rats.Compared with the operation + supine RIPK3 inhibitor group,the expression level of RIPK3 protein in the operation + prone RIPK3 inhibitor group decreased,but the difference had no statistical significance(P > 0.05),suggesting that the curative effect of prone position has certain advantages over supine position.Conclusion:PPV is effective in improving respiratory mechanics and reducing mortality in patients with ARDS caused by sepsis.PPV does not have adverse effects on hemodynamics and inflammation indices.The expression level of RIPK3 protein in ARDS model rats is high.RIPK3 inhibitor can effectively reduce the expression level of RIPK3 protein in ARDS model rats,and the therapeutic effect of prone position is better than that of supine position.