Abstract: Objective To investigate the effects of the intervention of Sonic Hedgehog(Shh)signaling pathway on learning and memory ability in rats with intrauterine growth restriction(IUGR)and its possible mechanism. Methods The rat models of IUGR were established by feeding with low protein diet during pregnancy, and their newborn rats were divided into model group, Shh signaling pathway inhibitor cyclopamine group(CYC group)and Shh signaling pathway activator purmorphamine group(PUR group), 20 rats in each group. In addition, 20 normal newborn rats in the same period were selected as the normal control group. After intervention, Morris water maze test was performed to detect the learning and memory ability of newborn rats at the age of 30 days. Immunofluorescence BrdU/NeuN double labeling method was used to detect the proliferation level of hippocampal neurons. TUNEL staining was used to observe the level of cell apoptosis in hippocampus. Spectrophotometry was used to detect the activity of Caspase-3 in hippocampus. Western blotting was used to evaluate the expression levels of Shh signaling pathway related protein Smoothened(Smo), Gli-1 and Bcl-2 in hippocampus. Results Compared with the normal control group, the ability of learning and memory and the proliferation level of hippocampal neuron in the model group were decreased(P<0.05), the apoptosis level of hippocampus and the activity of Caspase-3 were increased(P=0.028, P=0.029), while the protein expression levels of Smo, Gli-1 and Bcl-2 were reduced in hippocampal tissue(P=0.017, P=0.026, P=0.031). Compared with the model group, the ability of learning and memory and the proliferation level of hippocampal neuron in the PUR group were increased(P<0.05), the apoptosis level of hippocampus and the activity of Caspase-3 were decreased(P=0.033, P=0.045), and the protein expression levels of Smo, Gli-1 and Bcl-2 in the hippocampus tissue were increased(P=0.041, P=0.016, P=0.033). However, compared with the model group, the above indicators of rats in the CYC group were worse, and the difference was statistically significant(P<0.05). Conclusion Activation of Shh signaling pathway can improve the learning and memory ability of IUGR newborn rats by promoting the proliferation of hippocampal neurons and inhibiting cell apoptosis.

Key words: Sonic Hedgehog signaling pathway, Intrauterine growth restriction, Learning and memory ability, Neuronal proliferation, Apoptosis