17-AAG 对大鼠颈总动脉球囊损伤后内膜增生的影响及其作用机制.

Objective: To investigate the influence and possible mechanism of 17-Allylamino-17-emethoxy-geldanamycin (17-AAG) on the intimal hyperplasia after carotid artery balloon injury hi rats. Methods: Thirty-six male SD rats were divided into Sham group (n=12). BI group (n=12) and 17-AAG group (n=12) randomly. SD rats were injured using a 2F Fogarty balloon embolectomy catheter. 17-AAG group were disposed by intraperitoneal injecting 17-AAG at a dose of 20 mg/kg2d. After carotid artery balloon injuried 21 days, the damage area of the segment were harvested. HE staining was performed to observe the morphological changes of intima and to evaluate the degree of intimal hyperplasia. The expression of proliferating cell nuclear antigen (PC'NA) hi each group were by imniunohistocheniical staining to evaluate the proliferation of vascular smooth muscle cells. The degree of apoptosis of vascular smooth muscle cells in each group were detected by flow cytometry. Results: The results of HE staining showed that there were different degr ees of intimal hyperplasia following carotid artery injury in BI group and 17-AAG group. I'M ratio of BI group and 17-AAG group significantly increased than that of Sham gr oup (P<0.05). I'M ratio of 17-AAG group distinctly decreased than that of BI group (P<0.05). The results of hmiiunohistochemical staining showed that the expression of PC’NA in carotid artery in BI group and 17-AAG group were significantly higher than that hi Sham group (P<0.05). The expression of PC’NA in 17-AAG group was significantly lower than that in BI group (P<0.05). Compared with Sham gr oup, the apoptosis rate of vascular smooth muscle cells in BI and 17-AAG gr oup significantly increased (P<0.05). Compared with BI gr oup, the apoptosis rate of vascular smooth muscle cells hi 17-AAG group obviously increased (P<0.05). Conclusions: The results of the present study demonstrated that 17-A AG appeared to attenuate intimal hyperplasia after carotid artery balloon injury in rats. The possible mechanism of inhibition of neohithnal formation may be enhance the apoptosis rate of vascular smooth muscle cells. [ABSTRACT FROM AUTHOR]