| ObjectivePost-stroke depression(Post-stroke Depression,PSD)refers to the depressionsympto ms induced after stroke,and is one of the most common emotional disorders after stro ke.PSD has an important impact on the rehabilitation of neurological function,quality of life and survival rate of stroke patients,which obviously increases the economic bu rden of the patients themselves,families and society,so it is currently receiving more an d more attention[1].However,the pathogenesis of PSD is not very clear.The previous research of the research group found that the damage of hippocampus structure is clo sely related to the occurrence of PSD."Hippocampal nerve remodeling disorder" is its key step.JAK/STAT signaling pathway is widely involved in cell proliferation differenti ation and maturation,apoptosis and immune regulation,and JAK2/STAT3 are expresse d in hippocampal neurons and glial cells,which are closely related to neurodegenerati ve diseases,so this study is based on JAK2/STAT3 signaling pathway for PSD rats be havioral studies and hippocampal studies were conducted with a view to discovering t he correlation between JAK2/STAT3 signaling pathway and PSD and the intervention mechanism of YinaoJieyu Prescription(YNJYP)on PSDMethods270 male SPF-grade SD rats were randomly divided into normal group,sham oper ation group,stroke group,PSD group,western medicine group,and YNJYP group,each wit h 45 rats.The sham operation group only isolated blood vessels,and the stroke group o nly received MCAO.The PSD rat model was prepared by chronic restraint stress comb ined with single cage feeding in the PSD group,the western medicine group,and YNJY P group one week after MCAO.7days after the stroke model was established,western medicine group was given fluoxetine hydrochloride capsule 2.33 mg/(kg d),YNJYP gro up was given YNJYP 9.92 g/(kg d),and rats in other groups were given 10mL/kg disti lled water once a day.The following tests were performed at 2,4,and 8 weeks after str oke:1.Sucrose wvater test,open field test and forced swimming test to detect behavioral cha nges.2.Immunohistochemical method was used to detect the expression of P-JAK2 and P-ST AT3 in the | dentate gyrus of hippocampus.3.Western blot method to detect the expression of P-JAK2 and P-STAT3 in hippocamp Us.4.RT-PCR method was used to detect the expression of JAK2 and STAT3 genes in th e left hippocampus.Results1.Results of behavioral test1.1 Results of sucrose water preference testAt 2,4 and 8 weeks,compared with the normal group,there was no statistically sig nificant difference in sucrose water preference among the sham-operated rats(P>0.05).At 2 weeks,compared with the sham operation group,the sucrose water preference of rats in the stroke group decreased significantly(P<0.01);Compared with the stroke group rats,the sucrose water preference of the PSD group decreased(P>0.05);Compar ed with the PSD group,the sucrose water preference of rats in the western medicine g roup was significantly increased(P<0.05);the sucrose water preference of rats in the Y NJYP group was increased(P>0.05).At 4 weeks,compared with the sham operation group,the sucrose water preference of the stroke group was significantly reduced(P<0.05);Compared with the stroke gro up rats,the sucrose water preference of the PSD group was significantly decreased(P<0.05).Compared with the PSD group,the sucrose water preference of rats in YNJYP gr oup and western medicine group was significantly improved(p<0.01);At 8 weeks,compared with the sham operation group,western medicine group and YNJYP group,the preference of sucrose water in the stroke group decreased significant ly(P<0.01,P<0.05,P<0.05);Compared with rats,the sucrose water preference of the PSD group decreased(P>0.05);Compared with the PSD group,the sucrose water preference values of the YNJYP group and the Westem medicine group were significantly increa sed(P<0.01).At 2,4 and 8 weeks,there was no statistically significant difference in sucrose wat er preference between the western medicine group and the YNJYP group(P>0.05).1.2 Results of open field testAt 2,4 and 8 weeks,compared with the normal group,there was no difference in t he open field vertical and horizontal scores of the sham-operated group(P>0.05).At 2 weeks,compared with the sham operation group,the vertical and horizontal sc ores of rats in the stroke group decreased(P<0.01);Compared with the stroke group,th e vertical and horizontal scores of the rats in the PSD group decreased(P<0.05,P<0.05);Compared with the PSD group,the vertical score of rats in YNJYP group and weste n medicine group increased(P>0.05),and the horizontal score increased(P<0.O1,P<0.05).At 4 weeks,compared with the sham-operated group,the rats in the stroke group d ecreased vertically(P>0.05)and the horizontal score decreased(P<0.05);Compared wit h the rats in the stroke group,the vertical and horizontal scores in the PSD group dec reased significantly(P<0.01,P<0.05);Compared with the PSD group,thevertical and hor izontal scores of rats in the YNJYP group and the Western medicine group were signi ficantly increased(P<0.05;P<0.01).At 8 weeks,compared with the sham operation,the vertical and horizontal scores o f rats in the stroke group decreased significantly(P<0.01);Compared with the stroke g roup,the vertical and horizontal scores of the rats in the PSD group decreased(P>0.05);Compared with the PSD group,the vertical and horizontal scores of rats in YNJYP group and western medicine group were significantly increased(P<0.01).At 2,4 and 8 weeks,compared with the western medicine group,there was no signi ficant difference between the vertical and horizontal scores of the open-field rats in th e YNJYP group(P>0.05).1.3 Results of forced swimming testAt 2,4 and 8 weeks,compared with the normal group,there was no statistically sig nificant difference in the swimming struggle time of the sham-operated group(P>0.05).At 2 weeks,compared with the sham operation group,the swimming struggling tim e of the stroke group was shortened(P>0.05);Compared with the stroke group,the swi mming struggling time of the PSD group was significantly shortened(P<0.01,P<0.05);Compared with the PSD group,the swimming struggle time of rats in the western med icine group was significantly prolonged(P<0.05),and the swimming struggle time of ra ts in the YNJYP group was prolonged(P>0.05).At 4 weeks,compared with the sham operation group,the swimming struggling tim e in the stroke group was significantly shortened(P<0.01);Compared with the stroke g roup,the swimming struggling time in the PSD group was significantly shortened(P<0.01);Compared with the PSD group,the swimming struggling time of rats in YNJYP gr oup and western group was significantly prolonged(P<0.01);Compared with the stroke group,the swimming struggling time of rats in YNJYP group was obvious Prolonged(P<0.05).At 8 weeks,compared with the sham operation,the swimming struggling time of th e stroke group was significantly shortened(P<0.01);Compared with the stroke group,th e swimming struggling time of the PSD group was shortened(P>0.05);Compared with the PSD group,the swimming struggle time of rats in YNJYP group and western med icine group was significantly prolonged(P<0.01,P<0.05);Compared with stroke group,th e swimming struggle time of rats in YNJYP group was significantly prolonged(P<0.05).At 2,4,and 8 weeks,the swimming struggling time of the YNJYP group was not s ignificantly different from that of the Western medicine group(P>0.05).2.1 Results of molecular experriment2.1 Results of JAK2At 2,4 and 8 weeks,compared with the normal group,there was no difference in J AK2 immunohistochemistry,WB and PCR results in the sham operation group(P>0.05).At 2 weeks,compared with the sham operation group,the JAK2 immunohistochemi stry,WB and PCR results of the stroke group were significantly increased(P<0.05,P<0.05,P<0.01);Compared with the stroke group,the PSD group JAK2 immunity Histochemi cal,WB,and PCR results were not statistically different(P>0.05);Compared with the PS D group,the JAK2 immunohistochemistry,WB,and PCR results of the YNJYP group an d the Western medicine group were reduced(P<0.05,P>0.05,P>0.05).At 4 weeks,compared with the sham operation group,the JAK2 immunohistochemi stry,WB and PCR results were increased in the stroke group(P<0.05);Compared with the stroke group,the JAD2 immunohistochemistry in the PSD group,WB and PCR res ults were increased(P<0.05);Compared with the PSD group,the JAK2 immunohistoche mistry,WB and PCR results of the YNJYP group were significantly reduced(P<0.05,P<0.01,P<0.01);The JAK2 of the Western medicine group,immunohistochemistry,WB an d PCR results were significantly reduced(P<0.01,P<0.01,P<0.05).At 8 weeks,compared with the sham operation group,the JAK2 immunohistochemi stry,WB and PCR results of the stroke group were increased(P<0.05,P>0.05,P>0.05);C ompared with the stroke group,the PSD group JAK2 immunization group There were no differences in the results of chemical,WB and PCR(P>0.05);Compared with the P SD group,the JAK2 immunohistochemistry,WB and PCR results of the YNJYP group were reduced(P<0.05);The JAK2 of the Western medicine group,immunohistochemistry,WB and PCR results decreased(P<0.01,P<0.05,P<0.05).At 2,4 and 8 weeks,compared with the Western medicine group,there was no diffe rence in the JAK2 immunohistochemistry,WB and PCR results of the Chinese medicin e group(P>0.05).2.2 Results of STAT3At 2,4 and 8 weeks,compared with the normal group,there was no difference in S TAT3 immunohistochemistry,WB and PCR results in the sham operation group(P>0.05);At 2 weeks,compared with the sham operation group,the STAT3 immunohistochem istry,WB and PCR results of the stroke group were significantly increased(P<0.05,P<0.05,P<0.01);Compared with the stroke group,the STAT3 immunity of the PSD group Th ere were no statistical differences in histochemical,WB and PCR results(P>0.05);Com pared with the PSD group,the STAT3 immunohistochemistry,WB and PCR results of th e YNJYP group and the western medicine group were reduced(P<0.05,P>0.05,P>0.05).At 4 weeks,compared with the sham group,the STAT3 immunohistochemistry,WB and PCR results were higher in the stroke group(P>0.05,P<0.05,P>0.05);Compared wi th the stroke group,the STAT3 immunohistochemistry in the PSD group,WB and PCR results were increased(P<0.05);Compared with the PSD group,the STAT3 immunohist ochemistry,WB and PCR results of the YNJYP group were significantly reduced(P<0.05,P<0.01,P<0.01);Western medicine group the STAT3 immunohistochemistry,WB and PCR results were significantly reduced(P<0.05,P<0.01,P<0.05).At 8 weeks,compared with the sham operation group,the STAT3 immunohistochem istry,WB and PCR results of the stroke group were increased(P<0.05,P>0.05,P>0.05);Compared with the stroke group,the PSD group STAT3 immunization group,there was no statistical difference between the results of chemistry,WB and PCR(P>0.05);Compa red with the PSD group,the STAT3 immunohistochemistry,WB and PCR results of the YNJYP group were reduced(P<0.05);Western medicine group STAT3 immunohistoche mistry,WB and PCR results decreased(P<0.05,P>0.05,P<0.05).At 2,4 and 8 weeks,compared with the Western medicine group,there was no diffe rence in the STAT3 immunohistochemistry,WB and PCR results of the Chinese medici ne group(P>0.05).ConclusionsThe method of suture MCAO combined with restraint stress and orphanage can e stablish a stable PSD model at 4 weeks after operation.YNJYP has dual effects on pr evention and treatment of PSD.Excessive activation of JAK2/STAT3 signaling pathway It may hinder the process of hippocampal nerve remodeling in rats,and the therapeuti c effect of YNJYP may be related to inhibiting the expression of genes and proteins r elated to the JAK2/STAT3 signaling pathway and promoting hippocampal nerve remod eling. |
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