Expressions Of TGF-β1 And Its Receptors In Frontal Lobe Following Subarachnoid Hemorrhage In Rats And Neuroprotection Of Nimodipine

Part one: Experimental studies on the expressions of TGF-β₁ and its receptors in frontal lobe following subarachnoid hemorrhage in ratsObjective To investigate the expressions of TGF-β₁ (transforming growth factor-β₁) and its receptors (TβR I, TβR II) in frontal lobe following subarachnoid hemorrhage (SAH) in rats and to study the relationships with cerebral vasospasm (CVS).Methods 42 health male Sprague-dawley (SD) rats were assigned randomly into following groups: Normal group, Control group(injected normal sodium through cisterna magna only), SAH 1d group, SAH 3d group, SAH 5d group, SAH 7d group and SAH 14d group (n=6). Double autologus arterial blood injection through cisterna magna was underwent to estabalish SAH model in rats. The morphologic changes of basilar artery (BA) were examined with hemotoxylin and eosin (HE) staining, and the expressions of TGF-β₁ and TβR I , TβR II in frontal lobe following SAH at defferent time point were detected by immunohistochemistry method.Results Since 1st day after SAH, the pathological changes including arterial narrowing, thickness of arterial wall, degeneration of endothelial cells and smooth muscle cells can be observed and such changes progressed with time and were more obvious on 5th day and 7th day. The luminal inner diameters of BA on 5th day and 7th day after SAH were about 60% and 68% of the control group's respectively, and the wall thickness of BA were about double and 1.8 times of the control group's respectively. The expression of TGF-β₁ incresed contiuely in SAH group, and reached to the peak on 3rd day(50 times of control group or so), and deceased on 5th and 7th day(half of the peak level), while the expressions on 5th and 7th day were still more obervious than those of the control group( p<0.01), and the level on 14th day was similar to the control group. The expressions of TβR I incresed contiuely in SAH group( p<0.01), and reached to the peak on 5th and 7th day(3-5 times of control group), and decreased close to control group on 14th day. The expression of TβR II incresed oberviously since 1st day( p<0.01), and reached the peak on 3rd day, while decresed significantly on 5th and 7th day( p<0.01) , and the level on 14th day was similar to the control group.Conclusions 1. The pathological changes including arterial narrowing, thickness of arterial wall, degeneration of endothelial cells and smooth muscle cells suggests that CVS happens after SAH. 2. The expressions of TGF-β₁ and TβR I , II in frontal lobe after SAH have changed and been concerned with CVS suggests that TGF-β₁ and TβR I , TβR II may paticipate the patho-process of vasospasm.Part two: Effects of nimodipine on the expressions of TGF-β₁ and its receptors in frontal lobe following subarachnoid hemorrhage in ratsObjectives To investigate the effects of nimodipine on the expressions of TGF-β₁ and TβR I , TβR II in frontal lobe at different time points following SAH in rats.Methods After establishing SAH model of double blood injection though cisterna magna, the rats were assigned randomly into SAH group and ND group. The two groups then were equally assigned into 5 subgroups according to time points(1d, 3d, 5d, 7d and 14d, n=6). The rats of ND group were injected ND 2mg/kg through femoral vein after the second blood injection, then given ND 2mg/kg by intraperitoneal injection everyday. The morphologic changes of basilar artery (BA) were examined with hemotoxylin and eosin (HE) staining, and the expressions of TGF-β₁ and TβR I , TβR II in frontal lobe were detected by immunohistochemistry method.Results No significant difference of luminal inner diameter and thickness of BA between SAH group and ND group can be seen. Compared with SAH group, the expression of TGF-β₁ was more obvious on 5th day and 7th day after SAH( p<0.01), the percentage were 1.5 times or so of control group at the same time point; the expression of TβR I decresed obviously( p<0.01), the percentage were 0.9 times or so of control group at the same time point; while the expression of TβR II increased ( p<0.01), the percentage were 1.6 times and 1.5 times or so of control group respectively at the same time point; There was no significant difference of TGF-β₁, TβR I and TβR II on 1st, 3rd and 14th day between SAH group and ND group.Conclusions 1. There was no significant effect of ND on the pathological changes of BA. 2. ND may play neuroprotective role in ischemic brain tissue by increasing the expression of TGF-β₁ to inhibit the overload of Ca²⁺. 3. The adjustment of ND on the expression proportion of TβR I and TβR II in the ischemic frontal lobe may be one of the mechanism of its neuroprotection.