Objective: To observe the effect of Zhali Nusi Fang(ZLNF) intervening bone marrow mesenchymal stem cells (BMSCs) transplantation on synaptic structural plasticity in rats after cerebral ischemia reperfusion injury (CIRI). Method: SD rats were randomly divided into sham-operated group

model group

ZLNF group

BMSCs transplantation group and ZLNF combined with BMSCs groups. Middle cerebral artery occlusion (MCAO) model was duplicated with nylon thread

BMSCs were cultured and amplified by the whole bone marrow adherence method. Drugs were given to the rats by intragastric administration (14.6 g·kg-1·d-1)

BMSCs suspension solution was transplanted into rat brain through carotid artery. Brain was taken out at 1

3

7

14 days after transplantation. The changes of neuronal synaptic ultrastructure were observed by transmission electron microscopy

synaptophysin(SYN) and postsynaptic density protein-95(PSD-95)protein expressions were detected by Western blot. Result: The structure of synapses in sham-operated group was integrated

the presynaptic membrane and postsynaptic membrane were clear

the synaptic cleft was visible

and a lots of synaptic vesicles distributed equably. While in model group

the quantity ofsynapses were decreased

the structure was destroyed and the synaptic cleft was dim

the amount of synaptic vesicles was decreased and even disappeared. The quantity of synapses was increased

the structure was close to the normal

and the concave and U form synapses could be seen in ZLNF group

the synaptic vesicles were increased at 3

7

14 days in ZLNF group

the synaptic cleft became wider at 14 dayin ZLNF group

the changes of neuronal synaptic ultrastructure in transplantation groups were in keeping with ZLNF group

the damage of synapses in combination groups was significantly lower

the synapses increased

and many concave synapses could be seen at 7

14 days in combination groups

the synaptic vesicles were significantly increased. The SYN

PSD-95 expressions in model groups were obviously decreased when compared with the sham-operated group (P<0.01). Compared with the model group

the SYN expression was increased at 7 day group in ZLNF and transplantation and in all the combination groups (P<0.01)

the PSD-95 expression was increased at 3

7

14 days in ZLNF and transplantation and in all the combination groups (P<0.01). Compared with the transplantation groups

the SYN

PSD-95 expressions were increased in all the combination groups (P<0.01

P<0.05)

the PSD-95 expression was decreased at 3 day in ZLNF group (P<0.01). Compared with the ZLNF group

the SYN

PSD-95 expressions were increased in all the combination groups (P<0.01). Compared with the same time groups

the SYN expression at 3 day group in ZLNF

transplantation and combination groups was lower than other groups (P<0.01)

and the PSD-95 expression in all 7 day groups was higher than other groups (P<0.01)

the PSD-95 expression in all 14 day groups was higher than any 3 day group (P<0.01

P<0.05)

the SYN expression at 14 day was lower than that at 7 day in ZLNF

transplantation group (P<0.01). Conclusion: ZLNF could increase the synaptic structural plasticity obviously after the transplantation of BMSCs to CIRI

the effect was superior when using the combination of them

and its mechanism may be related to the regulation of the dynamic expressions of SYN and PSD-95.