Abstract: Objective  To explore the effect of recombinant tissue plasminogen activator(r-tPA) thrombolytic therapy with broadened therapeutic window on the cerebral infarct volume, microvessel density (MVD), and expression of adherence factors (ICAM-1 and VCAM-1) in acute cerebral infarction. Methods  A total of 216 SD rats were randomly divided into the control group, stroke group, rtPA 4.5h group and rtPA 6h group. Each group was randomly divided into three subgroups, and brains were drawn from the animals in each subgroup on the 1st, 3rd and 7th day. TTC staining was employed to observe cerebral infarct volume, immunohistochemical staining was used to observe MVD around ischemic core, and real time-PCR was used to detect the expression quantity of ICAM-1 and VCAM-1 mRNA around cerebral infarcts. Results  Compared with the stroke group, the cerebral infarct volume was obviously reduced in the rtPA 4.5h group and rtPA 6h group at each time point (P<0.01). The cerebral infarct volume increased with the thrombolysis time, with statistical differences between the rtPA 4.5h group and rtPA 6h group(P<0.05). MVD was higher in the rtPA 4.5h and rtPA 6h groups compared with the stroke group on the 3rd day (P<0.05), which was significantly higher on the 7th day (P<0.01). MVD of the rtPA 4.5h group and rtPA 6h group increased with time, and the increase was more significant on the 7th day than on the 3rd day (P<0.05). No change of MVD were found between rtPA 4.5h group and rtPA 6h group on the 1st, 3rd and 7th day (P>0.05). The ICAM-1 and VCAM-1 mRNA expressions of stroke, rtPA 4.5h and rtPA 6h groups started to elevate (P<0.01) on the 1st day after thrombolysis, which reached peak on the 3rd day (P<0.01), and remained significantly elevated on the 7th day (P<0.01). Compared to the stroke group, the ICAM-1 and VCAM-1 mRNA expressions of rtPA 4.5h group and rtPA 6h group were lower at each time point (P<0.05). As the thrombolysis time extended, the ICAM-1 and VCAM-1 mRNA expressions of rtPA 4.5h and rtPA 6h groups increased, with statistical differences between them(P<0.05). Conclusion  The thrombolysis therapy of broadened time window could reduce the infarct volume, increase the microvessel density and inhibit the expression of immune adherence factors, which offers a reliable theoretical basis for the thrombolytic therapy of stroke.

Key words: Cerebral infarction, Time window, Thrombolysis, Microvessel density, Adherence factors