Effects Of Pentoxifylline On Traumatic Spinal Cord Injury In Rats

Spinal cord injury (SCI) is a kind of severe neurotrauma, causing life-long disability. Presently, therapy for SCI is still limited and recovery level of injured nerve is still disappointing. Recent studies have shown inflammatory immunological response is extremely active and tumor necrosis factor (TNF)-alpha overexpress in the early stage of SCI, indicating TNF-alpha may participate in pathological process ofsecondary spinal cord injury. Inhibiting early inflammatory immunological response in SCI may be a new therapy to treating SCI. Pentoxifylline (PTX), an unselective phosphodiesterase inhibitor, has been used widely to treat vascular disease. Recent studies have shown it can inhibit the synthesis of TNF-alpha and improve microcirculation. Presently, the effects of PTX on the production of TNF-alpha and its protective effect on injured spinal cord have not been reported. This study is to investigate the effect of PTX on the early inflammatory immunological response following SCI and its possible mechanisim.Objective:To investigate the changes of tumor. necrosis factor-alpha and nitric oxide (NO), the inhibition of PTX on TNF-alpha and NO after SCI in rats. To study the mechanism of PTX to treating SCI and provideexpremental data for clinically treating SCI. Methods:In this study 146 male SD rats, weighting 220-280g, were offered by the animal center of Henan Medical University. They were divided at random into four groups: sham operated groups (SO group) 17 rats; injured group (IN group) 41 rats; injured and treated with pentoxifylline group (PTX group) 44 rats; injured and treated with methylprednisolone (MP group) 44 rats, injured and treated group also divided according to four time points into four groups. At each time point 8 rats were used for the examing of TNF-alpha.' At 8h and 24 h time point every 8 rats were used for the examing of NO, Ca2+, Mg2+ and H20. Ten rats were used for pathology.The SCI animal models were made by using an improved Allen's weight-drop device.Intraperitoneal (i.p) injection of 30mg/kg PTX were given to PTX group after injury, two times a day, and MP (30 mg/kg) were given to MP group immediately after injury.At each time point some measures were taken as follows:1) the level of TNF-alpha in injured cord with radioimmunoassay2) the level of NO in injured cord with nitrate reductase method3) the content of Ca2+, Mg2+, H20 at lesion site with atom absorption flame spectrum assay4) the histomorphometry of injured spinal cord tissue, the spinal cord in each group were stained with hematoxylin and eosin (HE), so as to observe the microarchitectureStatistical data were described as mean SEM. According to the statistical principle, data were compared with analysis of variance.Results:1) the content of TNF-alpha in injured spinal cordIN group was significantly higher than SO group (P<0. 05) ; PTX groupand MP group were significantly lower than IN group (P<0. 05); PTX group was significantly lower than MP group. It showed that the inhibiting effect of PTX on TNF-alpha is better than MP.2) the content of NO in injured spinal cordIN group was significantly higher than SO group (P<0. 05); PTX group and MP group were significantly lower than IN group (P<0.05). No statistically significant difference was identified between PTX group and MP group (P>0. 05) .Tt showed that the inhibiting effect of PTX on NO is as good as MP.3) the content of Ca2+ , Mgz+, H20 at lesion siteCa2+: IN group was significantly higher than SO group (P<0. 05); PTX group and MP group were significantly lower than IN group (P<0.05); MP group were significantly lower than PTX group(P<0.05). It showed that the inhibiting effect of MP on Ca2+ is better than PTX.Mg2+: IN group was significantly higher than SO group (P<0. 05) ; PTX group and MP group were significantly lower than IN group (P<0. 05 ); MP group were significantly higher than PTX group(P<0. 05). It showed that the rising effect of MP on Mg2+ is better than PTX.H20: IN group was significantly higher than SO gr...