关键词: 脂质体; 转化生长因子β; 基因; 细胞凋亡; 脑损伤

Abstract: Objective To investigate whether neuroprotective effect can be achieved by liposome mediatedtransforming growth factor-β1(TGF-β1) gene transfer to rat brain after transient focal cerebralischemia.Methods Transient focal cerebral ischemia in a rat model was produced by middle cerebral arteryocclusion (MCAO) for 1 hour. Reliable behavioral parameters were employed to detect successfulocclusion of the middle cerebral artery. The complex of plasmid contained LacZ marker geneand cationic liposomes were injected directly into the cerebrospinal fluid (CSF) of one group ofcontrol animals (n=18) immediately after MCAO. The other group of animals (n=18) was injectedwith liposome-TGF-β1 complexes. Five days after transfection, behavioral tests were employedto evaluate the neurologic deficits. Expression of β-galactosidase and TGF-β1 gene productswere detected by immunohistochemistry, reverse transcription polymerase chain reaction (RTPCR)and western blot analysis. Infarct volume and TUNEL-positive cells were counted. SemiquantitativeRT-PCR was used to examine the difference of caspase-3 mRNA between the twogroups.Results Liposome-mediated gene transfer of LacZ and TGF-β1 into the ischemic brain providedeffective expression of transgene. Compared with the control group, the neurologic functionof the rats injected with liposome-TGF-β1 complexes was significantly improved(P <0.01);infarct volume was smaller significantly(P <0.01); TUNEL-positive cells decreased significantly (P<0.01)and the expression of caspase-3 mRNA also decreased significantly.Conclusion Liposome-mediated gene transfer into the ischemic brain provided effectiveexpression of transgene after transient focal cerebral ischemia. Neuroprotective effect can beachieved by liposome mediated TGF-β1 gene tranfer which led to the inhibition of the activity ofcaspase-3. Gene transfer mediated by liposome may be a promising approach for the treament ofcerebral ischemia.

Key words: Liposomes; Transforming growth factor beta; Genes; Apoptosis; Brain ischemia