Rosiglitazone And Telmisartan Synergistically Prevents Loss Of Dopominergic Neurons By Inhibiting Brain Inflammation And Oxidative Stress In An Experimental Model Of Parkinson’s Disease

Objectives To observe the impacts of rosiglitazone and telmisartan on the expression of tyrosine hydroxylase(TH), ionized calcium binding adapter molecule1(iba-1), p47-phox and inducible nitric oxide synthase(i NOS) in the substantia nigra of Parkinson’s disease(PD) model mice, and investigate the protective effects and the possible mechanism of rosiglitazone in combination with telmisartan on dopaminergic(DA) neurons.Methods A total of 75 healthy male C57BL/6N mice were randomly divided into 5 groups, with 15 mice in each group, including model group, telmisartan group, rosiglitazone group, rosiglitazone and telmisartan combination group and control group. Mice in the model group were given intraperitoneal injection of MPTP(25mg/kg, dissolved by normal saline) once a day for 7 successive days. Mice in the telmisartan group were given telmisartan lavage pretreatment(40mg/kg) 4 hours prior to MPTP injection, once a day for 7 successive days. Mice in the rosiglitazone group were given telmisartan lavage pretreatment(4mg/kg) once a day for 7 successive days. Mice in the drug combination group were given half dose of telmisartan(20 mg/kg) and rosiglitazone(2 mg/kg) lavage pretreatment 4 hours prior to MPTP injection, once a day for 7 successive days. Mice in the control group were given intraperitoneal injection with the same amount of normal saline with the model group once a day for 7 successive days. Samples of mice were taken in each group 12 hours after the last injection. The quantity of TH positive neurons and the changes of p47-phox and i NOS immune-reactive cells in the substantia nigra area in each group were investigated by using immunohistochemistry; the expression levels of TH, iba-1, p47-phox and i NOS in the substantia nigra area were tested with Western blot; and the optical density analysis on quantity of immunohistochemistry positive cells and stripes of Western blot were carried out by using computer graphic analytic method. All data were processed for the statistical analysis by using the SPSS13.0 software.Results Compared with mice in the control group, mice in the model group showed the typical PD-like symptoms. The TH positive neurons were lost significantly and the protein levels were declined remarkably in the substantia nigra; while the iba-1, p47-phox and i NOS immunopositive cells and the protein levels were significantly increased in the substantia nigra. Compared with mice in the model group, the PD-like symptoms of mice in the rosiglitazone group were eased; and the quantity of TH immunopositive cells was increased to some extent compared with the control group and the decline of TH protein levels were also eased, as well as iba-1, p47-phox, i NOS positive cells and protein levels in the substantia nigra were also decreased. Compared with model group, the PD-like symptoms of mice in the telmisartan group were eased; the TH immunopositive cells were increased compared with the model group and the decline of protein levels was eased, aswell as iba-1, p47-phox, i NOS positive cells and the protein levels in the substantia nigra were decreased. Compared with the model group, the PD-like symptoms of mice in the drug combination group were eased significantly; the loss of TH immunopositive cells were declined significantly compared with the model group and the decline of protein levels was eased significantly. The iba-1, p47-phox, i NOS positive cells and the protein levels were obviously decreased in the substantia nigra.Conclusion Rosiglitazone in combination with telmisartan can protect the dopaminergic neurons via suppressing the expression of iba-1, i NOS and p47 in the substantia nigra in mice models, and the neuroprotective effects of rosiglitazone combination with telmisartan are better than that of single use rosiglitazone or telmisartan.