ABSTRACT
OBJECTIVE： To observe the effects of dihydroquercetin （DHQ） on hemorheology and other relevant related indexes in local cerebral ischemic injury model rats. METHODS： SD rats were randomly divided into sham operation group， model group， nimodipine group （positive control， 20 mg/kg） and DHQ low-dose， medium-dose and high-dose groups （15， 30， 60 mg/kg）， with 10 rats in each group. Administration groups were given relevant medicine intragastrically， sham operation group and model group were given constant volume of 0.4％ Sodium carboxymethyl cellulose solution， once a day， for consecutive 14 d. After last administration， local cerebral ischemic injury model was induced by bilateral common carotid artery ligation in other groups except for sham operation group. After 24 h of cerebral ischemia， histopathological changes of brain tissue in rats of each group were observed； the levels of hemorheology indexes [whole blood viscosity （low， medium and high shear）， whole blood reduced viscosity （low， medium and high shear）， plasma viscosity]， erythrocyte parameters （hematocrit， EAI， DI， IR）， coagulation function indexes （APTT， PT， TT， FIB） were detected. RESULTS： Compared with sham operation group， the cells in the brain tissue of model group were loose， the gap was obvious， and the neurons around the ischemic area were damaged obviously； the levels of whole blood viscosity， whole blood reduced viscosity， plasma viscosity， hematocrit， EAI， IR and FIB were increased significantly， while the levels of DI， APTT， PT and TT were decreased or shortened significantly （P＜0.05 or P＜0.01）. Compared with model group， above symptoms of administration groups were improved to different extents， whole blood viscosity， plasma viscosity， EAI and IR of nimodipine group， whole blood viscosity and hematocrit of DHQ high-dose group， plasma viscosity and EAI of DHQ groups， and IR of DHQ medium-dose and high-dose groups were decreased significantly； DI， APTT， PT and TT of nimodipine group， DI， APTT and TT of DHQ groups and PT of DHQ high-dose group were increased or prolonged significantly （P＜0.05 or P＜0.01）. There was no statistical significance in other indexes among those groups （P＞0.05）. CONCLUSIONS： DHQ can protect against local cerebral ischemic injury model rats， the mechanism of which may be associated with improving hemorheology indexes and coagulation function disorder.
ABSTRACT
This study was aimed to verify the hypothesis that Ge-Xia Zhu-Yu (GXZY) decoction protects liver from porcine serum-induced oxidative stress through the thioredoxin system.SD rats were randomly divided into the blank control group,model group,normal rat + GXZY decoction group,model rat + GXZY group.The rat autoimmune hepatic fibrosis model was induced with porcine serum by intraperitoneal injection (0.5 mL/each rat) twice a week.And GXZY decoction (7.37 g raw material/kg· d) was simultaneously administered daily by gavage.Lipid peroxidation (LPO) levels and thioredoxin reductase (TrxR) activity in liver tissues were determined by the colorimetric method.Polymerase chain reaction (PCR) was used to analyze the transcription factor nuclear factor erythroid 2-related factor 2 (Nfe2l2,previously known as Nrf2) mRNA expression.And the western blot was used to analyze the thioredoxin-1 (Trx1) protein expression and Akt phosphorylation in the liver.The results showed that compared to the model control group,the GXZY decoction group attenuated porcine serum-induced oxidative stress,as indicated by the LPO level,in liver tissues.Furthermore,GXZY decoction significantly enhanced TrxR activity,Trx1 protein expression,Nfe2l2 mRNA expression,and Akt phosphorylation (all P＜0.05).It was concluded that the strong antioxidant properties of GXZY decoction in the porcine serum rat model was due to the enhancement of the hepatic thioredoxin system via activating Akt-Nrf2 signaling pathway.The study results provided experimental evidences for the supporting of this hypothesis.
ABSTRACT
Objective To investigate the effect of exogenous murine interleukin-18 (IL-18) on early mouse collagen Ⅱ -induced arthritis (CIA). Methods Mice were injected intraperitoneallg IL-18 (0.2 μg/d) combination with IL-10 (0.1 μg/d), IL-4 (0.1 μg/d) and IL-12 (0.1 μg/d) daily for five days before the onset of CIA. The arthritis response was monitored visually by macroscopic scoring. Reverse transcription -polymerase chain reaction (RT-PCR) was employed to determine the mRNA expression of cytokine in patella with adjacent synovium in CIA mouse. Histology of knee was examined to assess the occurrence of cartilage destruction and bone erosion. Wilcoxon rank test was selected. Results IL-18/IL-4 treatment could slightly suppress the macroscopic score of arthritis, but a more pronounced amelioration was found in mice treated with the combination of IL-18 and IL-10 during early treatment. On 38 days after immunizatian macroscopic score in treated group (0.12±0.20) was significantly improves than in the control group (0.29±0.19, P<0.05). This resulted in both the suppression of macroscopic signs of inflammation and the reduction of cellular infiltrates in the synovial tissue, which provided the protection against cartilage destruction. Moreover, the expression of Thl cytokines [IL-18 (0.22±0.06), IL-12 (0.14±0.05)] and inflammatory cytokine [IL-6 (0.22±0.11)] was greatly inhibited both in the synovial tissue and in the articular cartilage in the treatment groups compared with those in the control groups (P<0.05). However, the mRNA levels of Th2 cytokines [IL-10 (6.35±0.12), IL-4 (3.57±0.13)] were up-regulated after IL-18/IL-10 treatment (P<0.05). Moreover, IL-18R (0.40±0.15) levels were down-regulated compared with those in the control group (P<0.05). T-bet mRNA levels were decreased in IL-18/IL-10 compared with the control group, and GATA-3 mRNA (5.71±0.11) levels were significantly higher than those in the control group (P<0.05). Conclusion Low dose IL-18/IL-10 treatment can inhibit Th1 cytokines expression and induce Th2 cytokines expression, which may be mediated not only by inhibiting Th1 responses through IL-18/IL-18R mechanism, but also by inducing anti-inflammatory mediators such as IL-10 and IL-4 through a GATA-3-dependent mechanism.
ABSTRACT
Objective To investigate the effect of exogenous murine interlukin-18 (mIL-18) on early and established murine coUagen-induced arthritis (CIA). Methods Mice were injected intraperitoneally with IL-18 (0.2 μg/mouse) daily for 5 days before or after the onset of CIA. The response was monitored visually by macroscopic scoring. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the mRNA expression of cytokines in patella with adjacent synovium in CIA mouse. Histolpgy of knee synovium was used to assess the occurrence of cartilage destruction and bone erosions. Results IL-18 alone had no effect on macroscopic score, occurrence of arthritis, advancement of histology on early stage of CIA. Moreover, expression of Th 1 cytokines and Th2 cytokines in the synovial tissue and" articular cartilage remained unchanged compared with the control group, however, a pronounced progression of histology was found in mice treated with IL-18 in estabhshed CIA. Forty-three days after immunization, the macroscopic score in the treated group (0.33±0.11 ) was significantly improved than in the control group (0.25±0.09) (P<0.05). Moreover, the mRNA levels of IL-10 and IL-18BP both in the synovial tissue and in the articular cartilage in the treated groups decreased significantly than those in the control groups (P<0.05). Conclusion Low dose mIL-18 alone has no effect on early stage CIA. But pronounced exacerbation is found in mice treated with IL-18 on established arthritis, which supports that IL-18 initiates this effect by inhibiting IL-10 and IL-18 BP.