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Effect of polydatin on neuronal damage and cognitive impairment in rats with schizophrenia by regulating Shh/Ptch1 pathway
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DOI   10.11656/j.issn.1672-1519.2026.02.11
Key Words   polydatin;sonic hedgehog;patched 1;schizophrenia;neuronal damage;cognitive impairment
Author NameAffiliation
TANG Rong Psychiatry Department, Tangshan Fifth Hospital, Tangshan 06300, China 
LI Jing Psychiatry Department, Tangshan Fifth Hospital, Tangshan 06300, China 
Abstract
    [Objective]To explore the effects of polydatin(PD)on neuronal damage and cognitive impairment in rats with schizophrenia (SZ)by regulating the sonic hedgehog(Shh)/Patched 1(Ptch1)pathway.[Methods]Dizocilpine Maleate(MK - 801)was used to construct SZ model rats. The rats that were successfully modeled were assigned into SZ group, L-PD group, H-PD group(intraperitoneal injection of 50 and 100 mg/kg of PD respectively), and PD+cyclopamine group(intraperitoneal injection of 100 mg/kg of PD+10 mg/kg of Cyclopamine), with 12 per group. Another 12 rats were served as the NC group. The control(NC)group and the SZ group were injected with the same amount of saline through the stomach and peritoneal cavity, once a day, and continuously administered for 14 days. The stereotypical behavior scores of rats in each group were detected. Morris maze was used to evaluate cognitive function in rats. The enzyme-linked immunosorbent assay(ELISA)kit was used to detect the levels of superoxide dismutase(SOD), malondialdehyde (MDA)in serum, and acetylcholinesterase(AchE), acetylcholinesterase transferase(ChAT), and acetylcholine(Ach)in hippocampal tissue. Hematoxylin-eosin(HE)staining was used to detect the pathological morphology of hippocampal tissue. Terminal deoxynucleotidyl transferase - mediated dUTP nick - end labeling(TUNEL)staining was used to detect neuronal apoptosis in hippocampal tissue. Moreover, Western blot was performed to measure the expression of Shh and Ptch1 proteins in hippocampal tissue.[Results]Compared with the SZ group, each PD administration group could successively reduce the score of stereotyped behavior, alleviate the damage of hippocampal tissue and neuronal apoptosis(P < 0.05), decrease the expression of MDA and AchE in serum(P < 0.05), increase the escape latency and the number of crossing platforms(P < 0.05), and increase the expression of SOD, ChAT and Ach in serum(P < 0.05). Compared with the SZ group, the PD treatment groups significantly increased the protein expression levels of Shh and Ptch1(P < 0.05). However, the PD + Cyclopamine group reversed the changes observed in the high - dose PD group(P < 0.05).[Conclusion]The improvement of neuronal damage and cognitive impairment in SZ rats by PD is related to the activation of the Shh/Ptch1 pathway.

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