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ObjectiveTo investigate the effect of Danzhi Xiaoyaosan on the phosphorylation of tau protein and different sites of glycogen synthase kinase-3β （GSK-3β） and phosphoseryl/suanyl phosphate protein phosphatase 2A （PP2A） in the hippocampus of rats with Alzheimer's disease （AD） and its mechanism. MethodThe rat model of AD was established by injecting okadaic acid into the bilateral hippocampus of 90 male Wistar rats in SPF grades. The rats with successful modeling were selected and randomly divided into model group， aricept group （0.5 mg·kg-1）， and Danzhi Xiaoyaosan high， medium， and low groups （17.55， 8.77， and 4.38 g·kg-1）， and then gavaged for 42 d， once a day. Morris water maze was used to detect the learning and memory ability of rats， Nissl's staining was used to observe the morphological structure of neurons in the hippocampus， and Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of tau protein， GSK-3β， and PP2A. Western blot was used to determine the protein expression levels of tau protein， GSK-3β， and PP2A. ResultAs compared with the control group， the learning and memory abilities of the rats in the model group were significantly decreased （P<0.01）， and the hippocampal CA3 region cells had abnormal structure， disorderly arrangement， and decreased number. The expression levels of GSK-3β mRNA， GSK-3β， p-GSK-3β-Tyr216， p-PP2A， and p-tau were increased in the model group as compared with the control group （P<0.01）， and those of p-GSK-3β-Ser9 and PP2A decreased significantly （P<0.01）. As compared with the model group， the learning and memory ability of the Aricept group and the Danzhi Xiaoyaosan groups were improved （P<0.05， P<0.01）， and the cell morphology and the number of hippocampal CA3 regions were better. The mRNA expression levels of PP2A and tau in the Aricept group were significantly up-regulated （P<0.05）， the mRNA expression level of GSK-3β was significantly down-regulated （P<0.01）， and the protein expression levels of GSK-3β， p-GSK-3β-Tyr216， and p-PP2A were down-regulated （P<0.05， P<0.01）， and the protein expression level of PP2A was significantly up-regulated （P<0.01）. As compared with the model group， the mRNA expression level of PP2A in the high-dose Danzhi Xiaoyaosan group was significantly up-regulated （P<0.01）， and that of GSK-3β was significantly down-regulated （P<0.01）， whereas the protein expression levels of p-PP2A， p-GSK-3β-Tyr216， and p-tau were down-regulated （P<0.05， P<0.01）， and the protein expression level of PP2A was significantly up-regulated （P<0.01）. As compared with the model group， the mRNA expression level of GSK-3β was significantly down-regulated in the medium-dose Danzhi Xiaoyaosan group （P<0.01）， the protein expression levels of GSK-3β， p-GSK-3β-Tyr216， and p-tau were down-regulated （P<0.05， P<0.01）， and the protein expression level of PP2A was significantly up-regulated （P<0.01）. As compared with the model group， the mRNA expression level of PP2A was significantly up-regulated in the low-dose Danzhi Xiaoyaosan group （P<0.01）， and that of GSK-3β was significantly down-regulated （P<0.01）， whereas the protein expression levels of GSK-3β and p-GSK-3β-Tyr216 were down-regulated （P<0.05， P<0.01）， and those of p-GSK-3β-Ser9 and PP2A were significantly up-regulated （P<0.01）. ConclusionDanzhi Xiaoyaosan can improve the learning and memory ability of rats with AD， and its mechanism may be related to the regulation of the activities of GSK-3β and PP2A protein-related sites and the phosphorylation of tau protein.
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The diseased location of rectal cancer in China is mainly in the middle and low rectum, and the proportion of young patients is increasing. As the surgical resection of primary tumor is still the cornerstone of rectal cancer treatment, it has become the hotspot in the treatment of low rectal cancer to preserve the anus after radical surgery. This paper reviews the research progress of sphincter-preserving treatment for low rectal cancer.
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Objective To investigate the protective role of dexmedetomidine in rats with endotoxin-induced acute lung injury (ALI).Methods Forty-eight adult male SD rats were divided into four groups (n=12 each) according to the random number table: control group, lipopolysaccharide (LPS) group, dexmedetomidine (DEX) treatment group and DEX pretreatment group.ALI was induced in rats by femoral intravenous injection of LPS (8 mg/kg).Rats in DEX treatment group was given DEX (50 μg/kg) for 2 minutes via the femoral intravenous injection 0.5 hour after LPS injection, followed by maintenance pump injection of DEX (5 μg·kg-1·h-1).Analogously, rats in DEX pretreatment group was given DEX (50 μg/kg) for 2 min via the femoral intravenous injection 0.5 hour before LPS injection, followed by maintenance pump injection of DEX (5 μg·kg-1·h-1).By contrast, control group received the same amount of normal saline intravenously.All rats were sentenced to death and their carotid blood samples were collected6 hours after all injections.Superior lobe of the right lung was examined under light microscope and the histologic findings were tested using the difusse alveolar damage (DAD) score.Middle lobe of the right lung was used to calculate the lung tissue wet/dry weight (W/D) ratio.Samples of collected carotid blood were taken to measure levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6.Bronchoalveolar lavage fluid (BALF) obtained from bronchoalveolar lavage was collected to measure levels of TNF-α and IL-6.Results Lung tissue injury was obvious after LPS injection and DAS score was improved as well.However DEX therapy reduced the lung damage as well as the DAD score, especially obvious in DEX pretreatment group (P0.05), but IL-6 in BALF was significantly lower in DEX pretreatment group than DEX treatment group (P0.05).Conclusion Either preoperative injection of DEX or DEX treatment has protective effect in rats with LPS-induced ALI, while preoperative injection of DEX has been proved to be more effective.
