| Purpose:To observe the effect of Congrong Shujing granules on the morphology of striatum and prefrontal cortical area and the expression of GDNF and PI3K/Akt signaling pathway-related proteins in the midbrain of rats with Parkinson's disease induced by rotenone,and to explore the neuroprotective effects of Congrong Shujing granules on rats with Parkinson's disease model and its effects in different brain regions in rats with Kinsen disease.Methods:The PD rat model was established with rotenone sunflower oil emulsion(1.5 mg/kg/d),and then the rats successfully modeled were divided into normal group,solvent group,model group,Congrong Shujing granules low-dose group,Congrong Shujing granules medium-dose group and Congrong Shujing granules high-dose group.The normal group was given no treatment.The rats in the solvent group were injected with the same dose of sunflower oil emulsion on the neck and back.The Congrong Shujing granules low,medium and high dose groups were given 0.242 g respectively Congrong Shujing granules at concentrations of 0.483g/kg,0.483g/kg and 0.966g/kg were treated by intragastric administration for 14 days.At the same time,the normal group and the solvent group were treated with equal volume of normal saline.Behaviour observations were carried out at the end of model building and 7 days and 14 days after drug intervention;HE staining and immunohistochemistry were used to detect the expression of rat striatum,prefrontal cortex,GDNF and PTEN protein,and WB method The expression of GDNF,PI3 K,p-PI3 K and PTEN protein in the above-mentioned brain regions.Results:1 Behavioural observations results1.1 Suspension test: after 14 days of modeling,the suspension scores of rats in the model group and the dosed groups were significantly decreased compared with the normal group(P < 0.01);after 7 days of drug administration,the scores of rats in the medium and high dose groups were increased compared with the model group(P < 0.05 or P < 0.01);after 14 days of drug administration,the scores of rats in the medium and high dose groups were increased compared with the model group(P < 0.05 or P < 0.01);after 14 days of drug administration,the scores of rats in the medium and high dose groups were increased compared with the model group(P < 0.05 or P < 0.01).(P<0.01).1.2 Walk-length test: After 14 days of modeling,the step length of rats in the model group and each dose group decreased compared with the normal group(P<0.01);after 7 days of drug administration,the step length of rats in the medium and high dose groups increased compared with the model group(P<0.01);after 14 days of drug administration,the step length of rats in the medium and high dose groups increased compared with the model group(P<0.01).2.HE staining changes2.1 2.1 Changes in the HE staining of the striatum: the arrangement,number and overall morphology of the striatal neurons of the rats in the normal group were normal,and the number of neurons in the striatum area of the model group was less than that of the normal group,and the arrangement and overall morphology occurred changes: The number of cells in the rat striatum after administration increased compared with the model group,and the overall morphology and arrangement were improved.The above changes were particularly obvious in the middle and high dose groups.2.2 Changes in HE staining of prefrontal cortex: The arrangement,number and overall morphology of neurons in the prefrontal cortex of rats in the normal group were normal.The number of neurons in the prefrontal cortex of the model group was less than that in the normal group,and the arrangement and overall morphology were less Good;the number of cells in the prefrontal cortex of rats after administration increased compared with the model group,and the overall shape and arrangement were improved.3 Immunohistochemical detection of GDNF and PTEN expression in different brain regions3.1 Changes in the expression of striatal GDNF and PTEN: After 14 days of administration,the expression of striatal GDNF was decreased(P < 0.01)and the expression of PTEN was increased(P < 0.01)in the model group compared to the normal group;compared to the model group,the expression of striatal GDNF was increased(P < 0.01)in the rat striatum in each administered group.The expression of PTEN was reduced(P < 0.01).3.2 Changes in the expression of GDNF and PTEN in the prefrontal cortex: 14 days after the administration of the drug,compared with the normal group,the expression of GDNF in the prefrontal cortex of rats in the model group was decreased(P < 0.01)and the expression of PTEN was increased(P < 0.01);compared with the model group,the expression of GDNF in the prefrontal cortex of rats in each administered group was increased(P < 0.01).PTEN expression in the prefrontal cortex was reduced(P < 0.01).4 WB method to detect changes in the expression of GDNF-PI3K-related proteins in different brain regions4.1Changes in the expression of GDNF-PI3 K related proteins in the striatum: 14 days after administration,compared with the normal group,the expression of GDNF and phosphorylated PI3 K in striatum of the model group was reduced(P < 0.01),and the expression of PTEN was increased(P < 0.01),and the phosphorylated PI3K/PI3 K ratio was decreased(P < 0.05);compared with the model group,the expression of GDNF protein in striatum was increased in the medium and high dose groups(P < 0.05 or P < 0.01),increased expression of phosphorylated PI3 K in the high dose group(P < 0.01),increased expression of phosphorylated PI3K/PI3 K ratio in the high dose group(P < 0.05),and decreased PTEN protein expression in each dose group(P < 0.05 or P < 0.01).4.2 Changes in the expression of GDNF-PI3 K related proteins in the prefrontal cortex: 14 days after administration,compared with the normal group,the expression of GDNF in the prefrontal cortex of the model group was reduced(P<0.01),and the expression of PTEN increased(P< 0.05);Compared with the model group: the expression of GDNF protein in the prefrontal cortex of rats in each treatment group increased(P<0.05 or P<0.01);the expression of PTEN protein in the prefrontal cortex of rats in the middle and high dose groups decreased(P<0.05).There was no significant difference in PI3 K and phosphorylated PI3 K and PI3K/PI3 K ratio in the prefrontal cortex of rats in each group(P>0.05).Conclusion:1.Congrong Shujing granules can improve the behavioral deficits of rats with PD model,promote the expression of GDNF-PI3 K signaling pathway-related proteins in striatum and frontal cortex regions of rats with PD model,and inhibit the expression of PTEN,and promote the activation of GDNF-PI3 K signaling pathway in striatum of rats with PD model.2.Congrong Shujing granules have neuroprotective effect on striatum and prefrontal cortex region of PD model rats,and the effect on striatum is more significant than that of the prefrontal cortex region.3.Congrong Shujing granules may play a neuroprotective role in different stages of PD by promoting the activation of striatum and frontal cortex GDNF-PI3 K signaling pathway and inhibiting the expression of PTEN. |
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