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Information Seminar Paper

Title

VENTILATOR INDUCED LUNG INJURY; MYOSIN LIGHT CHAIN PHOSPHORYLATION AND CLAUDIN 4 EXPRESSION IN RAT LUNG ARE THYROID DEPENDENT

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Abstract

 INTRODUCTION: ALTHOUGH MECHANICAL VENTILATION (MV) IS A LIFE-SAVING INTERVENTION IN ILL PATIENTS, IT CAN CAUSE LUNG DAMAGE REFERRED AS VENTILATOR INDUCED LUNG INJURY (VILI). EPITHELIAL/ENDOTHELIAL BARRIER DYSFUNCTION IS IMPLICATED IN VILI. INCREASED CLAUDIN 4 (CLUD 4), A TIGHT JUNCTION PROTEIN IS ASSOCIATED WITH LESS PERMEABLE BARRIERS. IN OTHER HAND INCREASED PHOSPHO MYOSIN LIGHT CHAIN (PP-MLC) MEDIATED BY MLC KINASE (MLCK) RESULTS IN LEAKY TIGHT JUNCTION PERMEABILITY. IN VITRO, THYROID HORMONES (THS) POTENTLY INHIBIT MLCK. THEREFORE, WE INVESTIGATED THE EFFECTS OF THYROID STATE IN VILI, LEVEL OF LUNG PP-MLC AND CLUD 4 EXPRESSION IN RAT.METHODS: THIS STUDY WAS DONE IN THREE MAIN GROUPS AS: EUETHYROID (EUE), HYPOTHYROID (HYPO) AND HYPERTHYROID (HYPER). HYPO AND HYPER STATE WERE INDUCED BY ADDING METHIMAZOLE AND LEVOTHYROXINE TO DRINKING WATER RESPECTIVELY. AFTER VERIFICATION OF THYROID STATE ALTERATIONS, VILI WAS INDUCED BY 2 HRS VOLUME CONTROLED MV. SEVERITY OF LUNG INJURY, PP-MLC, AND CLUD 4 EXPRESSION WERE ASSESSED THROUGH HISTOMORPHOLOGICAL, WESTERN BLOTTING AND IMMUNOHISTOCHEMISTRY STUDIES RESPECTIVELY.RESULTS: IN ALL ANIMALS MV APPLICATION RESULTED IN LUNG INJURY. HOWEVER, THE SEVERITY OF LUNG INJURY WAS SIGNIFICANTLY HIGHER IN HYPO AND LOWER IN HYPER AS COMPARED TO THAT IN EUE ANIMALS. LUNG PP-MLC WAS SIGNIFICANTLY INCREASED BY HYPO AND DECREASED BY HYPER STATES. SIMILARITY LUNG PP-MLC IN VENTILATED ANIMALS WAS SIGNIFICANTLY HIGHER IN HYPO AND LOWER IN HYPER AS COMPARED TO THAT IN EUE ANIMALS. MV INCREASED ALVEOLAR CLUD 4 EXPRESSION IN ALL ANIMALS, WITH HIGHER IN HYPO AND LOWER IN HYPER THAN THAT IN EUE ANIMALS.CONCLUSION: THYROID GLAND STATUS (SERUM LEVEL OF THS) MAY ALTER VILI SEVERITY THROUGH MODULATION OF THE EXPRESSION OF PROTEINS INVOLVED IN REGULATION OF JUNCTIONAL PERMEABILITY.

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