Effects of Astragalus Polysaccharides Nanoparticles on Cerebral Thrombosis in SD Rats.

OBJECTIVE: To investigate the efficacy and improvement of Astragalus polysaccharides (APS) and APS-nano on cerebral thrombosis in rats. METHODS: A total of 72 SD rats were randomly divided into NC group, Model group, APS-Nano group, and APS group. The cerebral thrombosis Model of SD rats was established by injecting compound thrombus inducer into the internal carotid artery. After 14 days of different intervention treatments, the TTC staining of brain tissue were performed, and A/left brain wet weight ratio, left brain/right brain wet weight ratio, blood rheology indexes, and coagulation function indexes of cerebral thrombosis were measured. ELISA was used to measure the contents of thromboxane 2 (TXB2), 6-keto-prostaglandin F1α (6-Keto-PGF1α), tissue factor (TF), neuron-specific enolase (NSE), S-100ß, catenin (CAT), superoxide dismutase (SOD), as well as malondialdehyde (MDA). The binding specificity between miR-885-3p and TF was verified by the double-luciferin reporting experiment, and western blot was used to measure the expression level of TF protein. RESULTS: Compared with the Model group, after treatment with APS-nano or APS, the ratio of left brain/right brain wet weight decreased significantly. Whole blood low shear viscosity (WBLSV), whole blood high shear viscosity (WBHSV), plasma viscosity (PV), and erythrocyte aggregation index (Arbc) was all reduced. In addition, prothrombin time (PT) and activated partial thromboplastin time (APTT) were increased, and fibrinogen (FIB) content was decreased. The expression of TXB2, 6-Keto-PGF1α, and TF showed a downward trend. Similarly, the expression of TF protein was decreased. Furthermore, the contents of NSE and S-100ß proteins were all decreased, whereas the contents of CAT and SOD were increased, and the contents of MDA was decreased. At the same dose, compared with APS treatment, APS-nano treatment had a significant inhibitory effect on cerebral thrombosis in rats. Finally, we found that TF is a target gene of miR-885-3p and specifically binds to miR-885-3p. CONCLUSION: APS has a significant inhibitory effect on the formation of cerebral thrombosis induced by compound thrombus inducers. Moreover, APS-nano has a more significant inhibitory effect on cerebral thrombosis. Meanwhile, the regulation of miR-885-3p regulating TF expression may be related to the occurrence of cerebral thrombosis.

[Expressions of aquaporin-4, matrix metallo-proteinase-2 and matrix metallo-proteinase-14 in peritumor edematous zone of glioma and clinical implications].

OBJECTIVE: To distinguish the expressions of matrix metallo-poteinase and aquaporin in peritumor edematous zone and normal brain tissue for different pathological levels of glioma and explore the relationship of glioma cell invasiveness and brain edema. METHODS: The immunohistochemical method of SP was employed to detect the expressions of aquaporin-4 (AQP-4), matrix metallo-proteinase-2 (MMP-2) and matrix metallo-proteinase-14 (MMP-14) in glioma and normal brain tissue. Due to a rarity of glioma Grades I and II, grades I and II glioma were pooled into low malignancy group (LMG) and grades III and IV into high malignancy group (HMG). The software program SPSS 11.0 was used for Kolmogorov-Smirnov test of independent samplets. The differences were detected between normal brain tissue and LMG and HMG. Also the relationship of AQP4, MMP-2 and MMP-14 was analyzed. RESULTS: With the advancing pathological grades of glioma, the expression of AQP-4, MMP-2 and MMP-14 were higher in positive areas. There were significant deviations among 3 groups. CONCLUSION: The expressions of AQP-4, MMP-2 and MMP-14 in normal brain tissue and all levels of glioma edema are positively correlated. And there is a close correlation between glioma invasiveness and edema extent.

Expression and antioxidation of Nrf2/ARE pathway in traumatic brain injury.

OBJECTIVE: To explore the expression of Nrf2/ARE pathway in hindbrain tissue after the traumatic brain injury (TBI) and its anti-oxidative stress effect in the secondary nerve injury. METHODS: The mice with Nrf2 gene knockout were used for the establishment of brain injury model. The experimental animals were divided into four groups: (Nrf2(+)/(+)) sham-operation group, (Nrf2(+)/(+)) brain injury group, (Nrf2(-)/(-)) sham-operation group and (Nrf2(-)/(-)) brain injury group. The specimen 24 h after cerebral trauma was selected. Then RT-PCR method was adopted to detect the expression of Nrf2 mRNA in brain; Western blotting method was adopted to detect the levels of Nrf2, HO-1 and NQO1 proteins in brain; ELISA method was adopted to detect the oxidative stress indicators: protein carbonyls, 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: The Nrf2 mRNA and protein of Nrf2(-)/(-) mice were not expressed, and the difference of the relative amount of Nrf2 mRNA between Nrf2(+)/(+) TBI group and Nrf2(+)/(+) sham-operation group was not statistically significant (P>0.05); the level of Nrf2 protein in Nrf2(+)/(+) TBI group increased significantly compared with the Nrf2(+)/(+) sham-operation group (P<0.01); in the sham-operation groups, the levels of HO-1 and NQO1 proteins of Nrf2(-)/(-) mice decreased obviously compared with the Nrf2(+)/(+) mice (P<0.01); after brain injury, the levels of HO-1 and NQO1 proteins of Nrf2(+)/(+) mice increased obviously compared with the corresponding sham-operation group (P<0.01); the levels of HO-1 and NQO1 proteins of Nrf2(-)/(-) mice in TBI group had no obvious change compared with the corresponding sham-operation group (P>0.05); there was only a little amount of expression of protein carbonyls, 4-HNE and 8-OHdG proteins in brain tissues in the Nrf2(+)/(+) and Nrf2(-)/(-) sham-operation groups, and the difference was not statistically significant (P>0.05); after brain injury, the three oxidative stress indicators were significantly up-regulated in the Nrf2(+)/(+) and Nrf2(-)/(-) groups, and the up-regulation of the latter group was more significant (P<0.01). CONCLUSIONS: After TBI the Nrf2/ARE pathway is activated and the activity of Nrf2 transcription regulation increases. However, the regulation dose not occur in the gene transcription level and only could increase the Nrf2 protein level, while the mRNA expression level has no obvious change. The nerve cell protective effect of Nrf2/ARE pathway in TBI achieves through inhibiting the oxidative stress injuries.