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Study Of ANP,CGRP On Mechanism Of AQP1 In Acute Injured Lung In Rats

Posted on:2005-02-10Degree:MasterType:Thesis
Country:ChinaCandidate:X F MiaoFull Text:PDF
GTID:2144360122490203Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The aquaporins (AQP) are family of homologous water-transporting proteins, which play an important role to keep fluid balance. Discovery of the aquaporin family of water channel proteins has provided a molecular explanation for rapid water movements across the plasma membranes of cells. To date, 10 mammalian member of the aquaporin water channel family have been identified. They are expressed in many tissues. The lung expresses several AQPs: AQP1, AQP3-5. Each of theaquaporin water channel proteins present in the lung has a unique distribution which suggests functional specialization. Movements of water in the lung involved in many physiology processes, whereas abnormal movements of water are found in clinical lung disorders such as acute lung injury, pulmonary edema. Therefore, to study the distribution, pathophysiology of aquaporins deeply in the lung will contribute to understand pathogenesis of acute lung injury. Acute lung injury (ALI) is a inflammatory disease which result in widely lung tissue injury and the multiple organ injury in the end caused by various reasons, promoted by many inflammatory cells and cytokines interaction. Over past years, we do lots of researches on treatment of ALI used by Atrial natriuretic peptide (ANP) and calcitonin gene-related peptide (CGRP). ANP and CGRP are hot hormones in recent years. They have strongly biological effects including vasorelaxation, improving microcirculation,inhibiting the release of inflammatory mediators and so on. They not only play a role in regulating important physiology functions, also preserve various tissues and organs. It has been proved in animal experiments that ANP, CGRP can treat ALI effectively, however, the mechanism is not identified. In this experiment, we established rat ALI model, used ANP, CGRP to treat ALI, observed expression changes of AQP1 in rat lung, and thereby to explore the mechanism of ANP, CGRP in the treatment of ALI.Method:Establish rat ALI model by injecting oleic acid into rats vein. Thirty-two rats were randomly divided into the flowing groups: normal control group, ALI model group, ANP treatment group, CGRP treatment group. Changes of AQP1 expression in the lungs of rats in each group were analyzed by immunohistochemistry and western blot. The blood air, lung wet/dry (W/D) weight ratio and pathological examination were measured in each group.Results:1. PaO2 in different group of rats Compared with normal control group (12.6+0.5Kpa) , PaO2 in ALI model group(8.7 + 0.8Kpa) decreased significantly, while PaO2 in ANP(10.3+1.0Kpa) CGRP treatment group(10.6 + 1.2Kpa) were higher than that in ALI model group.2. W/D in different group of rats In contrast to normal control group (4.07 + 0.16), W/D in ALI model group (4.52 + 0.18) were higher obviously, after treatment of ANP CGRP, W/D in ANP, CGRP treatment group decreased than that in ALI model group, which W/D were 4.25 + 0.14 and 4.22 + 0.21 respectively.3. AQP1 expression in different group of rats AQP1 express predominantly in microvascular endothelia and to a lesser extent in alveolar epithelia. AQP1 expression in ALI model group decreased dramatically paralleled with normal control group, while AQP1expression in ANP CGRP treatment group was higher than that in ALI model group.4. Western Blot result AQP1 protein electrophoresis straps in different group of rats differ in acreage and depth of color. AQP1 expression greyscale in ALI model group decreased markedly than that in normal control group, while AQP1 expression greyscale in ANP CGRP treatment group increased obviously than that in ALI model group.5. Pathological examination In ALI model group, leukocytes and lots of inflammatory cells infiltration, interstitial pulmonary edema pneumoconiosis and blood cells can be seen. In ANP CGRP treatment group, the lung histopathological displays markedly improved. In normal control group, alveolus structure is clear without effusion.Conclusion:1. After intravenous injection oleic acid (0.0...
Keywords/Search Tags:aquaporinl, acute lung injury, atrial natriuretic peptide, calcitonin gene-related peptide
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