Effects of atorvastatin on apoptosis and cytochrome c expression in perihematonla tissue after intracerebral hemorrhage in rats

Objective To investigate the effect of atorvastatin on cytochrome c （CytC） expression and neuronal apoptosis after intracerebral hemorrhage in rats. Methods A total of 108 male Sprague-Dawley rats were randomly allocated into 3 groups： sham operation group, saline control group, and atorvastatin group （n = 36 each group）. All the groups were redivided into 6 h, 12 h, day 1, 3, 5 and 7 time points （n =6 at each time point）. An intracerebral hemorrhage model was induced by using a modified two-step injection method. After modeling, atorvastatin was used for gavages （20 mg/kg, once a day） in the atorvastatin group. The saline control group was given the same volume of saline. Behavior evaluation was used for neurological score. TUNEL staining was used to detect apoptosis in perihematoma tissue. Immunohistochemical method was used to detect the CytC expression in perihematoma tissue. Results Behavior evaluation showed that the neurological scores decreased gradually with the passage of time in the atorvastatin group and the saline control group. There were no significant differences at 6 h, 12 h, day 1 and day 3, but the neurological scores in the atorvastatin group were significantly lower than those in the saline control group at day 5 （0. 50 ± 0. 55 vs. 1.50 ＋ 0. 55; t = 3. 162, P =0. 010） and day 7 （1.00 ±0. 63; t =2. 712, P =0. 022）. TUNEL staining showed that the numbers of apoptotic cells increased first and then decreased in the saline control group and the atorvastatin group. They reached the peak at 1 hour after modeling There were significant differences in the number of apoptotic cells in each group in perihematoma tissue at the same time point （all P = 0. 000）, and the significance in the saline control group was more than that in the sham operation group and the atorvastatin group （all P 〈0. 05）, but at day 7, there was no significant difference in the number of apoptotic cells between the atorvastatin group and the sham operation group （12. 69 ± 3.35 vs. 9. 33 ± 2. 07; P = 0. 148）. Immunohistochemical method showed that the numbers of CytC positive cells increased first and then decreased in the saline control group and the atorvastatin group, reached the peak at 12 h after modeling in te saline control group （68. 19 ± 11.93） and at 1 d in the atorvastatin group （35.64 ± 9. 12）. There were significant differences in the numbers of CytC positive cells in perihematoma tissue at the same time point in each group （P =0. 000）. The numbers of CytC positive cells in the saline control group was significantly more than that in the sham operation group and the atorvastatin group （all P 〈0. 05）, but there was no significant difference in the numbers of CytC positive cells between the atorvastatin statin group and the sham group at day 7 （16. 08 ± 3.80 vs. 13.67 ± 2. 94; P = 0. 349）. Conclusions Atorvastatin may inhibit the release of CytC of nerve cells in perihematoma tissue after intracerebml hemorrhage, and thus reduce CytC-mediated apoptosis and neurological deficit after intracerebral hemorrhage. Key words: Cerebral Hemorrhage;  Hydroxymethylglutaryl-CoA Reductase Inhibitors;  Atorvastatin;  Cytochrome c Group;  Apoptosis;  Rats