The Effects Of Endotoxemia On Lung Function, Kidney Function And The Expression Of Aquaporins In Rats

Objective:to research the expression changes of the relative damage index and theaquaporins (AQPs) in lung and kidney tissue in endotoxemia rats,to explore thefunction of AQPs in acute lung injury(ALI) and in acute kidney injury(AKI) and thepossible crosstalk mechanism between lung and kidney.Methods:48the two months male ofSPF wistar rats wererandomly divided into thenormal control group (NC) and the lipopolysaccharide group (LPS), Rats in LPSgroup was made into themodel of endotoxemia rats by lipopolysaccharide (5mg/kg)injection via caudal vein, the NC group was given the corresponding dose saline at thesame time.The groups rats were killed on the2h、6h、12h、24h after modeling success,the blood, lung and kidney tissue were collected, the lung was taken for observing themorphological changes, the lung function damage index was detected by the wet/dryweight ratio (W/D) and HE staining observing the lung pathology; the kidney damageindex was detected by the contents of UREA and CRE were measured by biochemicalanalyzer and HE staining observing the kidney pathology; the levels of plasma TNF-αwere measured by enzyme linked immunosorbent assay (ELISA); Real-Time PCRwas performed to inspect the mRNA expression levels of AQP1, AQP5of lung andAQP1of kidney; the protein expression levels of AQP1, AQP5of lung and AQP1ofkidney were detected by Western blot and immuohistochemical stainin.Results:1.Compared with NC groups, the W/D weight ratio of lung in LPS groupswas markedly increased on the2h、6h、12h(P0.01),12h increased the mostobviously;2.General observation of samples showed lung volume increasing in LPSgroup than NC group,6h,12h were the most obvious, there are some punctatehemorrhage on surface of lung tissue, for24h were the most obvious; HE stainingshowed lung tissue appearing obviously swelling changes on6h,12h in LPS group, appearing the pathological changes including haemorrhage and inflammatory cellsaggregation on12h,24h;3.Compared with NC groups,the contents of UREA and CREwere significantly increased in LPS group on each time point(P0.01,P<0.05);4. Thepathology of kidney tissues show that nephridial tubule appeared edematous changeson6h,12h after LPS modeling;5. Compared with NC groups,the contents of TNF-αwere significantly increased in LPS group on2h,6h,12h(P0.01,P<0.05);6.Compared with NC groups, the mRNA expression level of AQP1, AQP5of lung andAQP1of kidney were significantly down-regulated inLPS groups on each timepoint(P0.01);7.Western blot show that the protein expression levels of AQP1, AQP5of lung and AQP1of kidney were markedly decreased in LPS groups than in NCgroups on each time point(P0.01); Immuohistochemical stainin also show that theprotein expression levels of AQP1of lung and kidney were visibly diminished in LPSgroups than in NC groups on each time point;8. Correlation analysis: the positivelinear correlation were found among the mRNA expression level of AQP1, AQP5oflung and AQP1of kidney (P0.01); the mRNA expression level of AQP1, AQP5oflung were negative linear correlated with the W/D weight ratio of lung (P0.01); thenegativelinear correlation was found between the mRNA expression level of AQP1ofkidney and the contents of CRE (P0.01); the negative linear correlation were foundamong the mRNA expression level of AQP1, AQP5of lung, AQP1of kidney with thecontents of TNF-α(P0.01).Conclusion:1.Endotoxemiaearly damage the lung and kidney at the same time.2.Endotoxin can induce AKI and ALI,and result in expression changes of aquaporin,Aquaporin can be used as the early clinical monitoring index.3.the change of AQPsBetween lung and kidney has certain correlation under the acute lung injury of kidneyat the same time.4.Endotoxin can stimulate the release of TNF-α,and TNF-α probablyby affecting the change of aquaporin,further exacerbation of ALI/AKI.