Protective Effects Of Tetrandrine On Brain Cells In Phenobarbital-dependent And-withdrawn Rats

Objective: This study is to investigate the effects oftetrandrine (Tet) on brain cells in phenobarbital-dependant and-withdrawn rats, and explore the related mechanisms.Methods: The ratswere randomly divided into the control group, phenobarbital-dependantmodel group, and Tet-treated groups of low-, mid-, and high-dosages.Following drug withdrawn, the morphological changes of the frontal lobecells were examined by H&E staining. Immunohistochemical stainingwas applied to detect the apoptosis-related proteins of Bcl-2and Bax.RT-PCR and Western blot methods were applied to detect the mRNA andprotein expression levels of Bcl-2and Bax, respectively, in the frontallobe.Results: Our results indicated that Tet effectively reduced thewithdrawal symptoms, particularly the weight loss, inphenobarbital-dependent and-withdrawn rats, P<0.05. H&E stainingshowed that Tet significantly restored the histopathological changes inthese addicted rats, in a dose-dependent manner. Theimmunohistochemistry, RT-PCR, and Western blot analyses indicated thatTet treatment significantly increased the Bcl-2+brain cells(P<0.05), themRNA (1.38±0.19、1.16±0.14、0.96±0.09VS0.63±0.06）and proteinexpression（1.91±0.20、1.57±0.14、1.12±0.29VS0.95±0.12） levels ofBcl-2, and decreased the Bax+cells(P<0.05), the mRNA（0.55±0.06、0.85±0.10、1.06±0.12VS1.33±0.11）and protein expression（0.79±0.06、0.93±0.10、1.16±0.22VS2.52±0.21）levels of Bax, as well as elevated theratios of Bcl-2/Bax, in phenobarbital-dependent and-withdrawn rats. Tetcould inhibit the apoptosis in these addicted rats, in a dose-dependent manner(P<0.05). Conclusion:1、On a gradedly increased dosage scheduleof phenobarbital,Drug-admixed-food (DAF) is a feasible way to establishanimal model of phenobarbital physical dependence.2、Tet can alleviatethe phenobarbital withdrawal symptoms, and protect the brain cellsagainst apoptosis, which may be related to the regulation of the mRNAand protein expression levels of Bcl-2and Bax.