Study The Neuroprotection Of PPARγ Agonist Piolitazone And Its Dose-dependent Effect Following TBI

Objective: To study the neuroprotection role and its dose-dependenteffect of the PPARγ agonist pioglitazone following trauma brain injury(TBI) was characterized by determining the inflammation factors of TNF-αand IL-6mRNA expression, and PPARγ mRNA expression, and byobserving the brain tissue injury and the delayed neuronal death, as well asthe apoptosis of neurocytes, under the treatment of either the differentdoses of pioglitazone or T0070907(the antagonist of PPARγ) in ratsfollowing TBI.Methods: The rat models were established by Feeney,s free fallingdevice. The male SD rats were divided into eight groups, namely thenormal group; the sham operation group; the pioglitazone treatment groups(treated with the different dose pioglitazone at6h,12h,24,30h,36h,42hafter TBI including0.5mg/kg group,1mg/kg group,10mg/kg group); thecontrol group(treated with the same volume saline at the same time afterTBI); the T0070907group (treated with T00709071mg/kg at the sametime after TBI); the T0070907plus pioglitazone group (treated with T00709071mg/kg before half an hour injection pioglitazone1mg/kg, thetime in that inject pioglitazone1mg/kg is the same as the pioglitazonetreatment group). Using quantitative PCR to detect the expression ofPPARγ mRNA、TNF-α mRNA、IL-6mRNA；HE, TUNEL and Nissl’sstaining were employed at48h after TBI in order to observe the brain tissueinjury, the delayed neuronal death and the apoptosis of neurocytes.Results:1) Compared with the normal group and sham injured group,the control group TNF-α mRNA and IL-6mRNA expressions weresignificantly increased (P<0.01). Compared with the control group, a trendof dose-dependent reduction in TNF-α mRNA and IL-6mRNA levels wereobserved in the pioglitazone treatment groups (P<0.01);2)T0070907+1mg/kg pio group compared with1mg/kg pio group, theexpressions of IL-6mRNA and TNF-α mRNA significantly increased(P<0.05);3) Compared with the control group, PPARγ significantlyincreased only in10mg/kg pio group (P<0.01).4) By using HE, NISSL,TUNEL staining, compared with the normal group and sham group, thebrain tissue damage, the delayed neuronal death and apoptotic cells wereincreased significantly (P <0.01) in the control group, and consistently,compared with the control group the brain tissue damage, the delayedneuronal death and apoptotic cells were in turn to reduced withpioglitazone dose increasing (P <0.01) in the pioglitazone treatment groups,and the more serious injury was observed in T0070907+1mg/kg pio group than in1mg/kg pio group (P<0.01).Conclusion: In summary, pioglitazone can reduce the inflammationfactors expression, the brain tissue damage and the apoptosis of nerve cellsafter TBI, and its neuroprotection effect is the dose-dependent manner.