Study on the role of Cathepsin B and JNK signaling pathway in the development of cerebral aneurysm

Objective: To investigate the correlation between JNK signal and the apoptosis of VSMC as well as the expression of Cathepsin B and to explore the role of JNK signal in the development of cerebral aneurysm. Methods: Rat models of cerebral aneurysm were established and histopathologic changes of cerebral aneurysm and the apoptosis of VSMC were analyzed. Rat models were respectively subject to subcutaneous injection of Cathepsin B siRNA and JNK inhibitor SP600125. Western blot technique was used to detect the expression of proteins like Cathepsin B, Caspase-3. and p-INK. Spearman's rho was used to examine the correlation between p-JNK and Cathepsin B, as well as the expression of relevant proteins. Results: The success rate of modeling rats with cerebral aneurysm was 88.75%. After the respective injection of Cathepsin B siRNA, SP600125 and their combination, the cell densities of VSMC of rats with cerebral aneurysm all increased significantly (P<0.05 or P<0.01), but the apoptosis rate of VSMC decreased significantly (P<0.01). Compared with normal rats, the expression of Cathepsin B, Caspase-3 and p-INK in cerebral aneurysm models increased significantly. Effectively intervening Cathepsin B genes with Cathepsin B siRNA could significantly inhibit the expression of Cathepsin B and Caspase-3, but hardly influence the expression of p-JNK. JNK inhibitor SP600125 had no influence on the expression of Cathepsin B and Caspase-3, but effectively inhibited the expression of p-JNK. In cerebral aneurysm tissues, positive correlation was observed between the expression of p-JNK and Cathepsin B, the correlation coefficient was r=0.640. Conclusion: After the attack of cerebral aneurysm, proteins like Cathepsin B, Caspase-3 and p-JNK are all involved in the apoptosis of VSMCs. This process may be realized by Cathepsin B which activates the apoptosis mechanism of Caspase-3 and mediate the apoptosis of VSMC through the JNK signaling pathway. Therefore, silencing Cathepsin B gene or inhibiting the conduction through JNK signaling pathway can mitigate the apoptosis of vascular smooth muscle cells in cerebral aneurysm.