The Research Of Activation Of Cytosolic Phospholipase A2 Expression On Hypertensive Cardiac Remodeling

Objective To investigate the activation of cytosolic PLA2 on hypertensive heart remodeling, In this study, we used electron microscopy to observe 4-week-old SHR,8-week-old SHR,16-week-old SHR,24-week-old SHR left ventricular myocardial ultrastructure changes, around the regulatory pathway of the ERK1/2, we detected expression of cPLA2 of ERK1/2 downstream regulatory factors in left ventricular wall, and ventricular septal of different-week-old SHR by immunohistochemistry, and detected expression of p-cPLA2, p-MEK, p-ERK1/2 by Western-blotting, analysis cPLA2 involved in cardiac remodeling under high blood pressure of hypertension in the cell signal transduction,or not, to clarify further the possible regulatory mechanism of the role of ERK1/2 in cardiac remodeling of hypertension.Methods①24 Spontaneously Hypertensive Rats (SHR) were divided into four groups, which were 4-week-old group (SHR4), 8-week-old group (SHR8), 16-week-old group (SHR16), 24-week-old group (SHR24);②24 Wistar-Kyoto (WKY) rats were used as the control group: 4-week-old group (WKY4), 8-week-old group (WKY8), 16-week-old group (WKY16), 24-week-old group (WKY24). With HE staining, light microscope micrometer was used to measure 4 week-old SHR ,8 week-old SHR,16 week-old SHR,24 week-old SHR hearts remodeling changes, and observe histological changes, TEM is used to observe ultrastructure of myocardial, we detected expression of cPLA2 in left ventricular wall, and ventricular septal of different-age SHR by immunohistochemistry, and detected expression of p-cPLA2, p-MEK, p-ERK1/2 by Western-blotting. Results 1. blood pressure: blood pressure remained at normal levels in the Wistar-Kyoto rats(107.65±6.55mmHg). Arterial blood pressure was normal in SHR4, and significantly increased in SHR8, SHR16, SHR24, it was higher than blood pressure of the same old WKY rats significantly.(P<0.05). 2. The ratio of heart weight to body weight: Ages with the increase in week old, the ratio of heart weight to body weight increased in SHR and WKY rats, in each SHR group the ratio was significantly higher than that of the same age in the control WKY group;the relative thickness of the heart ventricular wall: The relative left ventricular wall thickness was significantly increased with increased week age in SHR, the inner and middle of left myocardium was obvious. The relative left ventricular wall of SHR16, SHR24 was significantly higher than SHR4(P <0.05); histological changes: The arrange of myocardial is neat, the basic structure is clear in WKY control group,correspondingly, the arrange of myocardial is disorder in the individual regional myocardial of SHR group, the volume and length of SHR myocardial cells are generally increased, occasionally two nucleuses. interstitial vascular wall of SHR myocardial was significantly thicker than the WKY group. 3. SHR myocardial ultrastructure: The pathological changes of myocardium ultramicrostructure in SHR mainly displaying abnormality of myocardium membrane, sarcoplasmic reticulum, intercalated disk, mitochondrion and etc. 4. The expression of cPLA2 in the different parts of the heart: Ages with the increase in week old, the positive immunostaining expression of p-PLA2 in SHR and WKY increased, the left ventricular wall: The positive rate of expression in SHR16, SHR24 were 76.38%, 78.56% in the inner, which were higher than positive rate of 51.52%, 53.74% in WKY16, WKY24; The positive rate of expression in SHR16, SHR24 were 75.03%, 82.03% in the middle ,which were higher than positive rate of 46.51%, 55.67% in WKY16, WKY24; The positive rate of expression in SHR24 was 78.53% in the outer, which was higher than positive rate of 56.74% in WKY24; the interventricular septum: The positive rate of expression in SHR24 was 50.12% in the left of ventricular septal , which was higher than positive rate of 29.87% in WKY24; Right of ventricular septal expression of the phosphorylation of cPLA2 was no significant difference between groups. 5. Western blot had the same result as immunohistochemical techniques of p-PLA2. 6. p-MEK in rats heart: The content of p-MEK protein in SHR24 heart is higher than SHR8, the content of p-MEK protein in SHR24 heart is higher than WKY24 rats. 7. p-ERK in rats heart: The content of p-ERK protein in SHR24 heart is higher than SHR8, the content of p-ERK protein in SHR24 heart is higher than WKY24 rats.Conclusion (1) The left ventricular hypertrophy is based in SHR cardiac remodeling. (2)Myocardial cells proliferation/apoptosis imbalance, myocardial vascular remodeling and myocardial fibrosis participate in the SHR cardiac remodeling together. (3) MEK1/2-ERK1/2 -cPlA2 pathway involved in SHR cardiac remodeling and cardiac muscle cell proliferation/apoptosis imbalance.