Effects Of Fluvastatin On The Proliferation Of ASMC In Rats And Airway Remodeling In Guinea Pigs

Asthma is chronic airway inflammation, characterized by poorly reversible airway obstruction and hyperactivity. A number of postmortem studies have shown that the mean value for the volume of airway smooth muscle (ASM) in patients who dies of asthma was more than 50% higher than in normal subjects. The thickening of ASM mass causing airway remodeling is an important abnormality responsible for hyperactivity; airway remodeling has been an important factor to the pathogenesis mechanism of asthma. Several recent studies have identified that the increased smooth muscle mass, which has been assumed as a result of sustained or intermittent increases in ASM tone in the past decades, is mainly due to hyperplasia not necessary to hypertrophy only. There have been widespread studies for the mechanism of asthma and how to prevent and cure it, and initial progresses have been gotten. Recently scholars havefound that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (HCRI) can not only decline the level of the cholesterol level in vitro, but also has significant inhibition to the proliferation of many cells, such as fibroblast, rat lymphocyte and kidney cell, the blood smooth muscle cell of human, ape and porcine, human peripheral lymphocyte, CHO-Ki cell, Swiss 3T3 et al. But there has no report about the effects of HCRI on the ASM. The studies of fluvastatin, a new fully synthetic HCRI, on the proliferation of airway smooth muscle cell (ASMC) away from rat and the airway remodeling model of guinea pig, in order to discover a new method for the therapy of airway remodeling of asthma patients.Method: (DASMC was stimulated by 10% PCS and histamine, then added fluvastatin with the concentration of 10~5mol ?L"1 and 10"4mol ?L"1. MTT assay, index of cell in division and cell count were used to analyze the effects of fluvastatin on the proliferation of ASMC. (2)Airway remodeling models of guinea pig were established, after fluvastatin was given by oral and inhaled, image analysis system was used to measure the thickness of the airway smooth muscle mass and the basement membrane.Results:(1) ㏕he proliferation of ASMC was observed after the stimulation of 10% PCS and histamine(OD value was 1.32?.03 stimulated by 10% PCS and 1.27?.02 stimulated by histamine on day 4), cultured with fluvastatin at the concentration of 10"5mol ?L"' and 10"4mol ?L"1, the OD value was obviously decreased(by 10"5mol ?L"1 fluvastatin, OD values were 0.66?.01 and 0.66?.01 respectively; by lO^mol ?L"1, OD values were0.31?.01 and 0.29?.01 respectively, PO.01). At the concentration of10"5mol ?L"1, fluvastatin inhibited ASMC proliferation by>30%; at the concentration of 10~4mol ?L"1, cell proliferation is entirely inhibited. There was a concentration-dependent inhibition to the cell proliferation. ㊣ndex of cell in division: Cultured under the normal condition, the index of ASMC in division was (10.4?.88)%; at the concentration of 10~5mol ?L"1, the index was (3.73?.93)%. There had significant difference between the two results (P<.01). At the concentration of 10~4mol ?L"1, few cells in S phase could be seen under the microscope. (3)Cell count: The counts of the groups treated with fluvastatin were much lower than the control group after several days. At the concentration of 10"5 mol ?L"1 and 10~4 mol ?L"1 fluvastatin, cell count were 17.23?.97><104 and 8.21?.59xl04 respectively, the control group was 38.10?.85><104(P<0.01). The results were in accord with MTT assay and index of cell in division, fluvastatin could inhibit the proliferation of ASMC.(2) After asthmatic models of guinea pig inhaled ovalbumin for three month, airway remodeling models were established. The mean thickness of airway smooth muscle and basement membrane in airway remodeling group were 95?3um and 17?um respectively, higher than that of asthma group 51?um and 9?um, also the control group of 50?um and 10?um(P<0.01), in accord with the pathology of airway remodeling.(3) With fluvastatin given, the layer of trachea ASM and...