The Effect Of The ALk5 To TGF-β1—ALK1—P-SMAD1 Pathway In Hippocampus Of Rats With Epilepsy Induced By Kainic ACID

[Objective] By Male Sprague-Dawley rats, whose taken for the epileptic model kindled by Kainic acid (KA), to observe the expression of the mRNA and the protein of the ALK1 receptor and it’s downstream molecules p-Smadl and study the function of ALK5 receptor to ALK1 receptor after the injection of ALK5 inhibitor (SB431542), in order to explore new targets for possible intervention of epileptic seizures.[Methods] Male Sprague-Dawley rats were taken for the epileptic model kindled by Kainic acid (KA) and divided into three groups randomly as KA control group (A)、ALK5 Inhibitor 3days groupn ALK5 Inhibitor 7days group (C). Besides, take sham rats for the normal control group. The normal control group and KA group were injected with saline in abdominal cavity for three days; The ALK5 Inhibitor 3days group rats intraperitoneally infused with ALK5 Inhibitor for three days, and the ALK5 Inhibitor 7days group rats for seven days. The expression of the mRNA and the protein of the ALKl receptor and p-Smadl in the rats hippocampus neurons were examined by RT-PCR and immunofluorescence histochemistry.[Results](1) immunofluorescence histochemistry:(i) The expression of he ALK1 receptor and p-Smad1 in KA group were rising(P<0.05) compared with normal control group in the real time quantitative PCR and immunofluorescence histochemistry analysis, in which ALK5 Inhibitor 3days group and ALK5 Inhibitor 7days group were decreasing (P<0.05)compared with KA group, (ii) Results of ALK1 protein expression are as followed:AOD was 0.11±0.05 for control group,0.17±0.04 for KA control group,0.11±0.05 for ALK5 Inhibitor 3days group,0.08±0.04 for ALK5 Inhibitor 7days group; (iii) Results of p-Smadl protein expression are as followed:AOD was0.07±0.03 for control group,0.12±0.04 for KA control group,0.09±0.02 for ALK5 Inhibitor 3days group,0.08±0.02 for ALK5 Inhibitor 7days group.(2) real time quantitative PCR:(i) The expression of he ALK1 gene and p-Smad1 gene in KA group were rising(P<0.05) compared with normal control group in the real time quantitative PCR, in which ALK5 Inhibitor 3 days group and ALK5 Inhibitor 7days group were decreasing (P<0.05)compared with KA group. (ii)Results of ALK1 gene expression are as followed:Expression quantity is 1.00±0.00 for control group,3.34±1.52 for KA control group, 0.94±0.81 for ALK5 Inhibitor 3days group,0.92±0.42 for ALK5 Inhibitor 7days group; (iii)Results of p-Smadl gene expression are as followed:Expression quantity is 1.00±0.00 for control group,1.93±0.72 for KA control group, 0.98±0.13 for ALK5 Inhibitor 3days group,0.95±0.06 for ALK5 Inhibitor 7days group.[Conclusions](1) After ALK5 Inhibitor was injected into the abdominal cavity, the expression of ALK1 receptor and p-Smadl decreased.(2) The passway TGF-βΓ-ALK5-p-Smad2/3 have an promoting effect on the passway TGF-β1-ALK1-p-Smadl/5.