The Effects Of Non-specific Immunomodulation On Left Ventricular Remodeling In Spontaneous Hypertensive Rats

Backgrounds:Hypertension is one of the main causes of chronic heart failure. Ventricular remodeling is thought as a milestone in the progression of chronic heart failure due to hypertension. Its histopathologic characteristic includes myocyte hypertrophy,loss and interstitial fibrosis. Recently, the change of extracellular matrix such as collagen quatity,type and quality has arosed considerable interests in cardiovascular fields. Previous studies showed that hemodynamic stimulus and hormonal factors play crucial roles in the progression of cardiac fibrosis during hypertension. Therefore numerous evidence showed that angiotensin convertion enzyme inhibitors,Angiotonin II type-1 receptor antagonists and aldosterone receptor antagonists could facilitate to control blood pressure and attenuate cardiac fibrosis. Interistingly, recent studies showed that these therapeutic benifits might be partly resulted from the effects of immunomodulation. There are several lines of studies showing that the immune system can be activated during hyprertension. It was characterd by high expression of some inflammatory factors such as chemotactic factors, adhesion molecules and cytokines. These activated cytokines have implicated to accelerate the progress of ventricular remodeling by stimulating the synthesis of matrix and collagen. Accumulating evidence suggest that the non-specific immunomodulation might be a new therapeutic strategy for attenuating left ventricular remodeling. The non-specific immunomodulating drug, triptolide has been used to rheumatism and other autoimmunity diseases for many years, but its effects on ventricular remodeling remains unclear.Objectives: To explore the effects and its underlying mechanism of non-specific immunomodulation of triptolide on left ventricular remodeling and cardiac function in spontaneous hypertensive rats (SHRs).Methods:12-month-old SHRs were divided randomly into 2 groups: SHR-T (n=10) and SHR-C (n=10), while12-month-old SD rats were used as negative controls (n=10). They were respectively intraperitoneal injected with TP (10μg·kg-1·d-1, SHR-T group), saline (1.0 mL·kg-1·d-1, SHR-C group) and saline (1.0 mL·kg-1·d-1, SD group) for 8 weeks. Systolic blood pressure was assessed with the tail-cuff methed before and after treatment every 2 weeks. Cardiac structure and function was assessed by echocardiography after treatment. The left ventricular mass was measured by electronic balance after treatment and the LVMI was also determined. The change of structure and shape in myocytes was observed with hematoxylin and eosin dying. The collagen content was determined with Masson specific dying and spectrophotometry technique. The localization of collagen I and collagen III protein in myocardium was investigated by immunohistochemistric assays. The serum levels of TNF-α,IL-1β,IL-6 and IL-10 were determined by radial immune assays.Results:1,SBP and LVMI in both SHR groups were much higher than that in SD group(P<0.01, P<0.01). After the treatment with triptolide, the SBP,LVMI had no significant change(P>0.05, P>0.05). 2,Compared with SD rats, Hematoxylin-eosin staining showed the cadiomyocytes hypertrophy, arranged confused in SHRs, after the treatment with triptolide, it showed no significant change. Apart of these, the myocardial collagen contents, the localization of collagen I and collagen III protein in myocardium and the ratio of I/ III in SHRs were significantly increased (P<0.01, P<0.01, P<0.01, P<0.01). After the treatment with triptolide, the myocardial collagen contents, the localization of collagen I protein in myocardium were significantly decreased (P<0.01, P<0.01), but still higher than the SD group(P<0.01, P<0.01), the localization of collagen III protein in myocardium was increased, but it showed no significant difference (P>0.05) , while the ratio of I/ III was significantly decreased (P<0.01). The echocardiography showed that both LVEF and FS in SHRs were lower than those in SD (P<0.05), after the treatment with triptolide, they were a little increased, but it showed no significant difference(P>0.05). 3,Compared with SD group, the serum levels of TNF-α,IL-1βand IL-6 in SHRs were significantly higher (P<0.01, P<0.01, P<0.01), while IL-10 was a little higher (P>0.05). After the treatment with triptolide, the serum levels of TNF-α,IL-1β,IL-6 were significantly decreased (P<0.01, P<0.01, P<0.01), while the serum level of IL-10 was increased, but it showed no significant difference (P>0.05).Conclusions:Triptolide have no significant effect on SBP or myocyte hypertrophy in SHRs. Triptolide could modulate serum levels of cytokines, attenuate cardiac fibrosis and improve cardiac function in SHRs.