ABSTRACT
Objective To evaluate the effects of intraperitoneal injection of sodium iodate on the physiological indexes and retinal histopathological characteristics of SD rats comprehensively. Methods A total of 64 rats were randomly divided into negative control group and model group, half male and half female. The model group was intraperitoneally injected with 6 mg/mL sodium iodate once at the dose of 10 mL/kg and the negative control group was injected with 10 mL/kg 0.9% NaCl once. The body weight of all surviving rats was detected on the day of injection (0 day) and the 2nd, 6th, 9th, 13th, 16th, 20th, 23rd, 27th, 29th, 36th, 43rd, 50th and 57th days after injection. On the 3rd, 7th, 21st, 28th, 41st and 62nd days after injection, the rats were randomly selected (12 rats in each group on the 28th day, and 4 rats in each group at other time points, those in each group were half male and half female) for serum biochemical indexes detection. The organs were dissected and weighed, and then the main organs and tissues were stained with HE, and the eyes were stained with HE and TUNEL. Blood routine indexes were detected on the 28th and 62nd day after injection. Results After injection of sodium iodate, 88% of the rats in the model group had transient loose stools. During the observation period, the body weight of the rats increased slightly and was more obvious in male rats. On the 28th day after injection, compared with the negative control group, the red blood cell volume (RDW) of female rats and blood urea nitrogen (BUN), reticulocyte count (Retic#) and reticulocyte percentage (Retic%) of male rats in the model group increased significantly (all P＜0.05). The white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and hematocrit (HCT) of male and female rats showed decreasing trends, but there were no significant differences between the two groups (all P >0.05). The thymus weight and coefficient of male rats in the model group were smaller than those in the negative control group except for the 7th day after injection, but there were no significant differences between the two groups (all P ＞0.05). Histopathological examination showed that the retina of the model group gradually developed from wavy changes to abnormal electrocardiogram (ECG)-like changes, with disordered arrangement of each layer, focal thinning of the outer nuclear layer, and apoptosis of the outer nuclear layer of the retina. The incidence of lesions, lesion score and the number of apoptotic cells in the model group were significantly higher than or more than those in the negative control group at the same time, and the difference between the groups on the 28th day was statistically significant (all P＜0.01). Conclusion In addition to retinal degeneration in rats, intraperitoneal injection of sodium iodate also had a certain degree of influence on serum biochemical and blood routine indexes, and also showed a slight slow growth of body weight and transient changes in fecal traits. Therefore, when using this model to evaluate drug safety, the effects of modeling reagents on animals should be paid to attention.
ABSTRACT
Objective:To comparatively observe the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the Lewis lung cancer mice and to explore the mechanisms of Rg3 and PEG-PLGA-Rg3 nanoparticle anti-cancer in vivo.Methods:Lewis lung cancer mouse model was established and 60 mice were randomly divided into 5 groups with twelve in each group:PEG-PLGA-Rg3 nanoparticles group (Rg3-N),PEG-PLGA group (PEG),Rg3 group (Rg3 ),normal control group (C),saline control group(NS),and received intragastric administration for 1 4 days.The weights of the mice were measured every 2 days and the weight curves were obtained.At the same time,the color pattern,activity and men-tal status were observed.The mice were sacrificed when the administration was over,and the effects of 20 (R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on tumor weight,and the tumor:weight ratios were analysed.In addition,the tumor microvessel density (MVD)was measured by immunohistochemi-cal staining with anti-CD31 antibody to compare the effects of Rg3 and PEG-PLGA-Rg3 nanoparticles on the tumor angiogenesis in vivo.Furthermore,the levels of such angiogenesis and proliferation factors as MMP-9,HIF-1 α,VEGF,Ki-67 were examined by RT-PCR,Western blot and immunohistochemistry to explore the internal molecular mechanisms of anti-tumor effects in vivo.Results:The trends of variation of the mice weights in NS group and PEG group were rising early but declining later.In contrast,the trends of the other three groups were rising early and became stable later.In comparison with NS group, the mice of Rg3 group and Rg3-N group had better general status:brighter color,more active and better spirit.Compared with NS group,the tumor weight in PEG group,Rg3 group and Rg3-N group showed no significant difference but the tumor:weight ratio and MVD in Rg3 group and Rg3-N group declined signi-ficantly (P <0.01 ).Besides,there was no significant difference between Rg3 group and Rg3-N group. At the same time,the level of VEGF mRNA,the protein expression of MMP-9,HIF-1 α,VEGF in Rg3 group and Rg3-N group decreased compared with NS group.Furthermore,the level of each index above-mentioned in Rg3-N group was lower than that in Rg3 group.The expression of Ki-67 in PEG group,Rg3 group and Rg3-N group showed no significant difference compared with NS group.Conclusion:Rg3 and PEG-PLGA-Rg3 nanoparticle may suppress the expression of VEGF,MMP-9 and HIF-1 αin Lewis lung cancer mice,thereby indirectly contributing to their antitumor effects and alleviating the mice’s general status.In addition,PEG-PLGA nanoparticles embedding can promote Rg3 antitumor effect in vivo.