| Acute respiratory syndrome(ARDS)is an acute diffuse lung injury and subsequent acute respiratory failure caused by various risk factors,including in and out of the lung.The main pathological features are uncontrolled inflammation in the lungs or in the body,leading to increased pulmonary microvascular permeability,alveolar exudation of protein-rich fluids,followed by edema and transparent membranes,often accompanied by alveolar hemorrhage.It has been found that the levels of serum N-terminal pro-brain natriuretic peptides(NT-pro BNP)in patients with ARDS have significantly increased.Since NT-pro BNP and Brain natriuretic Peptide(BNP)are secreted by equal moles,the increase in the level of NT-pro BNP can reflect the increase of BNP to some extent.Recently more and more studies have found that renin-angiotensin system(RAS)plays an important role in the development of ARDS,and BNP is a natural antagonist of RAS.We first explored the role of the change of the levels of serum NT-pro BNP in patients with ARDS,and then explored the effect and mechanisms of recombinant human brain natriuretic peptide(rh BNP)on rat models with lipopolysaccharide(LPS)-mediated ARDS.To explore the role of the change of the levels of serum NT-pro BNP in patients with ARDS,and explore the effect and mechanisms of rh BNP on rats models with LPS-mediated ARDS.Objective:Methods:Part One A total of 36 ARDS patients admitted to ICU of the first affiliated hospital of Guangxi University of Traditional Chinese Medicine were selected.The patients were admitted to ICU as the starting point,and the patients were cured and discharged from ICU or died within 28 days of admission as the end,eliminating cases of abandonment or voluntary discharge.According to the outcome,ARDS patients were divided into survival group and death group.The hemodynamics of patients with ARDS was monitored by pulseindented continuous cardiac output(PICCO),and the values of extravascular lung water index(EVLWI)and pulmonary vascular permeability index(PVPI)were recorded at the time of entering ICU,in ICU 24 h and in ICU 48 h.The serum NT-pro BNP and C-reactive protein(CRP)were detected at the time of entering ICU,in ICU 24 h and in ICU 48 h.At the same time,the blood gas analysis of patients was detected when they were admitted to ICU.NT-pro BNP,CRP,EVLWI and PVPI were compared between survival and death groups,and the correlation between NT-pro BNP and oxygenic index(OI),NT-pro BNP and CRP,NT-pro BNP and EVLWI was separately analyzed with two-variable Pearson correlation analysis.Part TWO The rat models with ARDS were replicated by intraperitoneal injection of LPS.The effect of different dosage rh BNP on the survival rate of 6h and 12 h of rats with ARDS were observed and the wet/dry weight ratio of lung tissue in rats with ARDS were measured.The histopathological and ultrastructural changes of lung in rats with ARDS were separately observed by hematoxy-eosin staining(HE)and electron microscopy.The effect of different dosage rh BNP on lung apoptosis in rats with ARDS was detected by terminal deoxynucleotide transferase mediated notch endmarker(TUNEL).The gene and protein expression of inflammatory factor interleukin-1β(IL-1β),interleukin-6(interleukin-6)and TNF-alpha(TNF-α)in lung tissue of rats with ARDS were specially detected with real-time quantative-PCR(RT-PCR)and enzymatic immunoassay(ELISA).The protein level of Angiotensin II(Ang II)and Angiotensin1-7(Ang1-7)in lung tissue of rats with ARDS were separately detected with enzymatic immunoassay(ELISA).The effects of different dosage rh BNP on the protein expression of angiotensin converting enzyme(ACE)and angiotensin converting enzyme2(ACE2)in lung tissue of rats with ARDS were observed by immunohistochemistry(IHC).Results:Part One The levels of NT-pro BNP in the death group were significantly higher than that in the survival group at each time(P<0.01),but there was no significant difference in CRP levels between the two groups(P>0.05).The results of PICCO monitoring showed that both EVLWI and PVPI were higher than normal range in patients with ARDS.EVLWI of entering ICU and in ICU 48 h in the death group was significantly higher than that in the survival group(P<0.01,P<0.01).PVPI in the death group was significantly higher than that in the surviving group in ICU 48h(P<0.05).There was no linear correlation between the serum levels of NT-pro BNP and OI(r=-0.228,P>0.05),the serum levels of NT-pro BNP and CRP (r=0.085,P>0.05),but positive correlation with EVLWI and the serum levels of NT-pro BNP(r = 0.774,P<0.01).Part TWO Both low and high dosage rh BNP significantly reduced pulmonary edema in rats with ARDS(P<0.01,P<0.01)and decreased the mortality rate of rats with ARDS in 12h(P<0.05).The results of HE staining and electron microscopy shows that both low and high dosage rh BNP significantly improved the pathological damage of lung tissue。Both low and high dosage rh BNP significantly decreased the rate of lung cell apoptosis in rats with ARDS(P<0.01,P<0.01).Low and high dosage rh BNP not only inhibited the expression of inflammatory factor IL-1β(P<0.01,P<0.01)and TNF-α(P<0.01,P<0.01)gene in lung tissue of rats with LPS-induced ARDS(P<0.01,P<0.05),but also reduced IL-1β and TNF-α protein levels(P<0.01,P<0.01).Although the effects of low and high dosage of rh BNP on IL-6 gene expression in lung tissue were not statistically significant(P>0.05,P>0.05),and the effect of low dosage rh BNP on the level of IL-6 protein in lung tissue was also not statistically significant(P>0.05),high dosage rh BNP significantly decreased the level of IL-6 protein in lung tissue(P<0.05).Although there was no statistically significant effect of low dosage rh BNP on the levels of Ang II and Ang1-7 proteins in lung tissue of rats with ARDS(P>0.05,P>0.05),high dosage rh BNP significantly inhibited the level of Ang II protein(P<0.05)and significantly increased levels of Ang1-7protein(P<0.05)in lung tissue of rats with ARDS.Both low and high dosage rh BNP significantly inhibited expression of ACE protein(P<0.01,P<0.01)and increased expression of ACE2 protein(P<0.05,P<0.05)in lung tissue of rats with ARDS.Conclusions:(1)The serum levels of NT-pro BNP in patients with ARDS are positively correlated with pulmonary edema,and early dynamic joint monitoring serum NT-pro BNP,EVLWI and PVPI is valuable to evaluate the prognosis of patients with ARDS.(2)Local homeostasis imbalance of RAS in lung exists in rats with LPS-induced ARDS.rh BNP can improve the inflammation of lung tissue and pulmonary cells apoptosis by regulating the local homeostasis of RAS in rats with ARDS,thus reducing pulmonary edema. |
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