چکیده (انگلیسی):

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-JNK. 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-JNK 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.