ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of PEGylated IL-11 mutein (PEG-mIL 11) with different dose or injection frequency on thrombocytopenia in myelosuppressed mice and to compare its effect with mIL-11, so as to provide reference data for clinical use.</p><p><b>METHODS</b>Myelosuppressive model with thrombocyopenia was produced in BALB/c mice by whole bodyCo γ-ray irradiation in dose of administration 2.5 Gy followed by i.p. injections of carboplatin at 50 mg/kg. In study of injection frequency, 30 thrombocytopenic BALB/c mice were randomly divided into 5 groups: vehicle control group (once daily on d1, 4, 7), mIL-11 group [200 µg/(kg·d)×9 d], PEG-mIL 11 A group [111800 µg/(kg·d)×1 d (d 1)], PEG-mIL 11 B group 900 µg/(kg·d)×2 d (d 1,5), and PEG-mIL 11 C group [600 µg/(kg·d)×3 d (d 1,4,7)]. The route of administration is subcutaneous injection. The platelet counts were monitored in the subsequant 5 weeks. In study of dose administration, 100 thrombocytopenic BALB/c mice were randomly divided into 5 groups: vehicle control group (once daily on d1 and 5), mIL-11 group 200 µg/(kg·d)×9 d, and PEG-mIL 11 low-, mid-, and high-dose groups (200, 420 and 900 µg/(kg·d)×2 d, once a day on d1 and 5). The route of administration is subcutaneous injection. The platelet counts were monitored every 2-3 days in the subsequant 5 weeks, and CFU-Meg was determined on d 8 of the bone marrow cells collection.</p><p><b>RESULTS</b>AfterCo irradition and carboplatin injection, Plt level decreased with time, and a >80% reduction was noted at nadir when comparing with baseline. In frequency of administration study, the platelet nadir of the 3 PEG-mIL 11 groups were significantly higher than that of vehicle control and mIL-11 groups (P<0.05), while no significant difference was noted among the 3 groups of different administration frequences; In dose level study, the reduction of Plt count at the nadir in the 3 PEG-mIL 11 groups was significantly less than that of vehicle control and mIL-11 groups (P<0.05). And a rapid recovery of Plt count was found in the PEG-mIL 11 groups with a dose-dependent increase of Plt count on d 10. A lower reduction and a rapider recovery of RBC was also found in the PEG-mIL 11 groups. No significant effect on WBC was found for all the treatment groups. An increase in CFU-Meg was observed in PEG-mIL 11 and mIL-11 groups, with higher CFU-Meg in PEG-mIL 11 groups.</p><p><b>CONCLUSION</b>A preventive effect of PEG-mIL 11 on thrombocytopenia in myelosuppressed mice has been confirmed. In comparison with mIL-11, a better effect of PEG-mIL 11 is obtained under lower dose frequency, indicating a better compliance of the treatment regimen, and providing a foundation for developing a long-acting preparation of rhIL-11.</p>
ABSTRACT
Objective To observe the anti-atherosclerosis (AS) mechanisms of Shuxinwenban granules by observing its effects on the serum level of MMP-9, the expression of VEGF and the formation of the plaques in rabbits. Methods Totally 40 healthy female and male rabbits were divided into control group, model group, Shuxinwenban granules group and Simvastatin group. Control group was treated with basic diet, and other groups were treated with high cholesterol diet for 12 weeks to make AS rabbit models. The treatment groups were given corresponding drugs by gavage for 4 weeks. The serum levels of MMP-9 in rabbits were detected by double antibody sandwich enzyme-linked immunosorbent method and the surface density of VEGF in the atherosclerotic plaques by immunohistochemical staining, at the same time, the pathological changes of the aorta and atheroclerotic plaques were observed. Results Compared with the model group, Shuxinwenban granules significantly decreased the serum levels of MMP-9, and the difference was statistically significant (P <0.01). Similarly, Shuxinwenban granules could significantly decrease the surface density of VEGF in atherosclerotic plaques, the difference was also statistically significant (P<0.01). Pathology showed that the intervention of Shuxinwenban granules decreased the area of atherosclerotic plaque, caused the plaque to smaller and thinner. Conclusion Shuxinwenban granules blocked the inflammatory response by inhibiting the expression of VEGF in atherosclerotic plaque and decreasing the levels of MMP-9 in serum, which lessened the formation of the atherosclerotic plaques.
ABSTRACT
Objective To investigate the changes of serum myelin basic protein (MBP) and S100B orotein (S100B) in premature infants with periventricular leukomalacia (PVL) and their outcomes.Methods Seventy-eight premature infants with PVL (PVL group)and 43 normal infants (control group)who were hospitalized in our hospital from Nov 2007 to Jul 2008 were enrolled in the study.The infants were sampled for MBP and S100B levels on 1st,3rd,7th and 14th d after birth.Thirty normal infants and 69 infants with PVL were followed up every three months as they discharged until they were one year corrected age and their development quotients(DQ) were measured using Gesell development schedules.Results ( 1 ) The serum MBP levels increased on day 1 [ (7.61 ± 1.78 ) μg/L ],peak on day 3 [ ( 14.53 ± 3.12 ) μg/L],and then decreased.The serum MBP levels in infants with PVL group were significantly higher than those of control group at 1st,3rd,7th and 14th d after birth ( P ＜ 0.05 ).(2) The serum S100B levels increased on day 1,day 3 and day 7 [ (3.82 ±0.68),(4.41 ±0.91,),(5.78 ± 1.54) μg/L],peaked on day 7,and then decreased.The S100B levels of infants in PVL group were significantly higher than those of control group at 1st,3rd and 7th d after birth (P ＜0.05) ;and decreased on day 14 (P＞0.05).(3) Infants whose MBP and S100B levels increased at 7th day after birth had significantly decreased DQ than those of normal infants ( P ＜0.05 ).Conclusion The serum MBP and S100B levels in infants with PVL are correlated with the severity of central nervous system injury.If the serum S100B and MBP levels of PVL infants continues to rise more than 7 d,the DQ are lower,and the outcomes are poor.