ABSTRACT
Objective:To treat mice with Alzheimer's disease （AD） with β-catenin RNA interference （RNAi） Huangjingwan （HW）， so as to explore the neuroprotective signal mechanism of its prevention and treatment of AD. Method:A total of 81 male Kunming mice were randomly divided into normal control group， sham model control group， AD model group， Donepezil group， HW+scrambled group， HW+RNAi group， HW group， with 8 mice in each of donepezil group and HW group， and 13 mice in each of other groups. The AD models were established through injection with D-galactose and scopolamine in the last 5 groups for 5 consecutive weeks. On the 1st day of the 4th week after modeling， 0.75 μL PEI-LMW/β-catenin siRNAs nano-complex was injected into the right lateral ventricle of each mouse in for one time to treat with β-catenin RNAi in mice brains of the HW+RNAi group. The 0.75 μL complex was injected into the right lateral ventricle of each mouse for one time as for β-catenin interference control of the HW+scrambled group. The 0.75 μL normal saline was injected into the right lateral ventricle of each mouse in one time of the sham control group. Two weeks after intracerebroventricular injection， β-catenin RNAi was confirmed to be successful， and Donepezil （6.5×10-4 g·kg-1） was intragastrically administered to each mouse of donepezil group. HW （2.5 g·kg-1） was intragastrically administered to each mouse of HW group， HW+RNAi group and HW+scrambled group. Normal saline （0.5 mL·d-1） was intragastrically administered to each mouse of the sham control group. All gastric perfusion lasted for 4 weeks. At the end of gavage， the difference in learning and memory ability of mice was evaluated by platform jumping test. Nissl staining was used to count the number of neurons in s1Tr area of cerebral cortex and CA1 and CA3 areas of hippocampus of each mouse in each group. The mRNA expressions of Wnt1， DVL2， GSK-3β， β-catenin and CyclinD1 in mice brain of each group were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Western blot was used to detect the expressions of Wnt1， DVL2， GSK-3β， β-catenin and CyclinD1 in mice brain of each group. Result:The expression of β-catenin could be significantly inhibited through the injection with PEI-LMW/β-catenin siRNAs nano-complex into the lateral ventricle of AD mice， and nearly no β-catenin expression could be detected， which successfully achieved gene silencing. Compared with the normal control group， mice in AD model group showed that the learning and memory performance decreased significantly， the number of jumping errors increased （P<0.01）， the number of neurons in S1Tr area of cerebral cortex and CA1， CA3 areas of hippocampus decreased significantly （P<0.01）， the mRNA and protein expressions of Wnt1， DVL2， β-catenin， CyclinD1 in brain decreased significantly （P<0.01）， while the mRNA and protein expressions of GSK-3β increased significantly （P<0.01）. Compared with the AD model group， mice in HW group showed that the learning and memory performance increased significantly， the number of jumping errors decreased， the number of neurons in S1Tr area of cerebral cortex and CA1， CA3 areas of hippocampus increased significantly， the mRNA and protein expressions of Wnt1， DVL2， β-catenin， CyclinD1 in brain increased significantly， while the mRNA and protein expression of GSK-3β decreased significantly （P<0.01）. Compared with the HW group， mice in HW+RNAi group showed that the learning and memory performance decreased significantly， the number of jumping errors increased significantly （P<0.01）， the number of neurons in S1Tr area of cerebral cortex and CA1， CA3 areas of hippocampus decreased significantly （P<0.01）， there was no significant change in mRNA and protein expressions of Wnt1， DVL2， GSK-3β in the brain， and the mRNA and protein expressions of β-catenin， CyclinD1 decreased significantly （P<0.01）. Conclusion:HW can treat and prevent AD by activating Wnt/β-catenin signal pathway.
ABSTRACT
Alzheimer's disease （AD） is a neurodegenerative disease that leads to progressive memory and cognitive impairment and behavioral disorders， which has seriously threatened the health of the majority of middle-aged and elderly people. Traditional Chinese medicine （TCM） believes that the basic pathogenesis of AD is deficiency of kidney-essence， blood stasis and meridian stagnation. In recent years， many studies have shown that TCM has obvious value and advantages in the prevention and treatment of AD by multi-target mechanism. Therefore， it is of great significance to screen out effective anti-AD drugs from TCM compound prescriptions. Huangjingwan， also known as Jiuzhuan Huangjingwan， has the effects in tonifying kidney-essence， activating blood and removing stasis， with a potential effect in preventing AD. In this article， the feasibility of Huangjingwan in the prevention and treatment of AD was analyzed and discussed from the perspective of TCM theory， the study results of Huangjingwan in the prevention and treatment of AD were summarized， and the mechanism of its action was analyzed from the perspective of pharmacological mechanism. Based on TCM theory， Huangjingwan has the effect of anti-AD. According to relevant findings， Huangjingwan has many targets， such as anti-oxidation， anti-inflammatory， decrease of the level of oxidative stress in brain， activation of Wnt/β-catenin signal transduction in brain， regulation of glycogen synthase kinase-3β （GSK-3β）， protein phosphatase 2A （PP2A） activity balance， reduction of amyloid β （Aβ） content and tau protein hyperphosphorylation in brain， so as to exert effects in improving neurological symptoms and increasing learning and memory ability， with an anti-AD neuroprotective function. This will provide new ideas for in-depth studies and clinical applications of Huangjingwan against AD.
ABSTRACT
Objective::To observe the effect of Huangjingwan (HW) on antioxidant functions and β-amyloid 1-42 (Aβ1-42) and amyloid precursor protein (APP) expressions in the brain of Alzheimer' s disease (AD) rats. Method::SD rats were randomly divided into normal control group, sham model control group, AD model group, and low, medium, high-dose (equivalent raw drug dose 1, 3, 9 g·kg-1·d-1) HW groups.The AD models were established through intraperitoneal injection with 1.25% D-galactose (120 mg·kg-1·d-1, 6 consecutive weeks) and then one-time right ventricular injection with Aβ1-42 (10 μg). Two weeks after modeling, the rats in each HW group received corresponding drugs through intragastric administration, once a day, while the rats in sham model control group, AD model group were given normal saline 1 mL through intragastric administration, once a day.Gastric perfusion lasted for 8 weeks.At the end of the experiment, learning and memory abilities of the rats were assessed by Platform Jumping Test.The changes of physical endurance in rats were tested by 10% weight swimming under load.The activities of superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GSH-Px) antioxidant enzymes and the contents of glutathione (GSH) and malondialdehyde (MDA) in rat brain tissue were detected by colorimetry.The changes of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), Aβ1-42 and APP protein in rat brain tissues were determined by enzyme linked immunosorbent assay (ELISA). Western blot analysis was used to measure the expression of APP protein in rat brain. Result::Compared with the normal control group, rats in AD model group showed an obvious dementia state, that is more lying and less movement, longer learning response time, significant increase in the number of learning and memory errors, significant attenuation in physical fitness, significant decrease in the activities of antioxidant enzymes (SOD, GR, GSH-Px) and anti-inflammatory factors GSH in brain, significant rise in the levels of inflammatory factors MDA, IL-1β and TNF-α and the content of Aβ1-42 protein, and significant reduction in the content of APP protein in brain (P<0.01). Low, medium and high-dose HW could ameliorate dementia symptoms in AD rats, improve the achievement of learning and memory, antagonize body weakness and increase physical fitness, promote SOD, GR, GSH-Px activities and anti-inflammatory factor GSH level in the brain, reduce the levels of MDA, IL-1β and TNF-α in the brain, decrease the level of Aβ1-42 and increase the level of APP protein in the brains of AD rats compared with the AD model group (P<0.05, P<0.01), besides, within the dose range of 1-9 g·kg-1·d-1, HW has a more obvious effect with the increase of dose. Conclusion::HW has the effects in preventing and treating AD, which is related to the HW' s mechanisms in enhancing the function of antioxidant system in brain, reducing neuroinflammatory reaction and deposition of Aβ1-42 induced by oxidative stress, and maintaining the expression level of APP protein.
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<p><b>OBJECTIVE</b>To evaluate the usefulness of contrast-enhanced ultrasonography (CEUS) in the diagnosis of biliary diseases.</p><p><b>METHODS</b>CEUS was performed in 57 patients with biliary diseases. The contrast enhancement characteristics and the morphologic features were observed. The ultrasonographic results were compared with those obtained through conventional 2-D ultrasound (2D-US), color Doppler flow ultrasound (CDFI), and clinical, surgical, and laboratory findings. In some cases, the ultrasonographic results were also compared with those obtained from contrast-enhanced computed tomography (CECT).</p><p><b>RESULTS</b>The diagnostic accuracy of 2D-US combined with CEUS was significantly higher than that of 2D-US combined with CDFI 87.7% vs 71.9%; chi(2) = 4.41, P < 0.05). CEUS clearly showed the presence/absence of blood supply in biliary lesions and offered real-time imaging of the microcirculation perfusion in the lesions. It also offered useful information to differentiate biliary tumors from stones, bile mud, and/or blood clots. It distinctly displayed the size and contour of the lesions as well as the infiltrated range, depth, and the involved area. However, CEUS is most useful in reflecting blood perfusion patterns; it had limited value in differentiating the malignancies of polypoid lesions. The diagnostic accuracy (87.0% vs 91.3%;chi(2) = 0. 45, P > 0.05) and the size and range of the lesions displayed (0.4-6.2 cm vs 0.4-6.0 cm, P = 0.721) were not significantly different between CEUS and CECT.</p><p><b>CONCLUSION</b>CEUS is a useful tool in the routine ultrasonography of biliary diseases.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Biliary Tract Diseases , Diagnostic Imaging , Sensitivity and Specificity , UltrasonographyABSTRACT
<p><b>OBJECTIVE</b>To explore the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of renal cystic lesion.</p><p><b>METHODS</b>Totally 88 patients with 97 atypical cystic lesions of kidneys were examined by conventional ultrasound (color Doppler flow imaging and power Doppler flow imaging), CEUS, and contrast-enhanced computed tomography (CECT), respectively. The results from the three imaging approaches were classified by Bosniak classification system and compared with each other. In patients who underwent surgeries, the pathological results were used to validate the imaging results.</p><p><b>RESULTS</b>The results of CEUS and CECT on atypical cystic lesions were not significantly different (P > 0.05). The results gained by conventional ultrasound were significantly different from those of CEUS and CECT (P < 0.05). Compared with the pathological results of 32 patients who underwent surgery, the sensitivities of CEUS in the diagnosis of benign, doubtfully malignant, and malignant cystic tumors of kidney were 63.2%, 95.0%, and 94.7%, respectively, the specificities were 92.9%, 76.9%, and 85.7%, respectively, and the accuracies were 75.8%, 87.9%, and 90.0%, respectively.</p><p><b>CONCLUSIONS</b>The classification of atypical cystic lesions using CEUS is highly consistent with CECT. CEUS is valuable in the diagnosis of benign and malignant renal cystic lesions.</p>