1.Dihuang Yinzi Improves Cognitive Function of Mouse Model of Learning and Memory Impairments by Regulating Synaptic Plasticity via SIRT2
Wenting WANG ; Yangjing HAO ; Wenna SU ; Qinqing LI ; Shifeng CHU ; Junlong ZHANG ; Wenbin HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):9-17
ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine (SCOP) and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups: control (0.9% NaCl, n=10), model (SCOP 1 mg·kg-1·d-1, n=10), low-, medium-, and high-dose Dihuang Yinzi (SCOP 1 mg·kg-1·d-1 + Dihuang Yinzi 5.5, 11.0, and 22.0 g·kg-1·d-1, n=10), and donepezil (SCOP 1 mg·kg-1·d-1 + donepezil 0.84 mg·kg-1·d-1, n=10). Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week, and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week, 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 (SIRT2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor 1 (GluA1), protein kinase A (PKA), cAMP response element-binding protein (CREB), phosphorylated-CREB (p-CREB), postsynaptic density protein 95 (PSD95), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin (DCX) in the hippocampal dentate gyrus (DG) region. ResultsCompared with the control group, the model group showed impaired learning and memory (P<0.01), obvious neuronal damage in the hippocampal CA1 region, a reduction in neuron survival (P<0.01), a decrease in DCX expression in the hippocampal DG region (P<0.01), down-regulated proteins levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 in the hippocampal tissue (P<0.05, P<0.01), and an up-regulated protein level of SIRT2 (P<0.01). Compared with the model group, the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory (P<0.05, P<0.01), while the low-, medium-, and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival (P<0.05, P<0.01). The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression (P<0.05, P<0.01). The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 (P<0.05, P<0.01) and down-regulation in the protein level of SIRT2 (P<0.01). ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2, activating the PKA/CREB signaling pathway, improving synaptic plasticity, and reducing hippocampal neuronal damage.
2.Effect of Dihuang Yinzi Decoction (地黄饮子)on Retinal Insulin Content and Insulin Signaling Pathway Related Protein Expression in Alzheimer's Disease Model Mice
Dongyan WU ; Wanwei GUI ; Xiaodan WANG ; Qinqing LI ; Jinmiao CHAI ; Junlong ZHANG
Journal of Traditional Chinese Medicine 2024;65(15):1593-1601
ObjectiveTo observe the possible mechanism of Dihuang Yinzi Decoction (地黄饮子) for improving cognitive dysfunction in Alzheimer's disease (AD) from the perspective of retina. MethodsForty-five APP/PS1 mice (AD model mice) were randomly divided into model group, Dihuang Yinzi Decoction group, and memantine group, with 15 mice in each group, while 15 wild-type C57BL/6J mice from the same litter were used as blank group. Mice in Dihuang Yinzi Decoction group were given Dihuang Yinzi Decoction 30.03 g/(kg·d) by gavage, mice in the memantine group were given memantine hydrochloride 6.1 mg/(kg·d) by gavage, and mice in the blank group and the model group were given normal saline 2 ml/(kg·d) by gavage for 4 consecutive weeks. Fasting blood glucose was measured weekly. After 4 weeks of intervention, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed; Morris water maze was used to detect the changes in spatial memory ability of mice; glucose oxidase method was used to detect retinal glucose content of mice; enzyme-linked immunosorbent assay (ELISA) was used to detect serum and retinal insulin content of mice, and Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was performed to observe the histopathological changes in the retina, and the retinal thickness and ganglion cell number were counted; protein immunoblotting was performed to detect the retinal pathway-associated proteins [insulin receptor substrate 1 (IRS1), phosphorylated insulin receptor substrate 1 (pIRS1), phosphatidylinositol-3-hydroxykinase (PI3K), protein kinase B (Akt1), phosphorylated protein kinase B (pAkt1)] expression; retinal glucose transporter protein 4 (GLUT4) expression was detected by immunohistochemistry. ResultsCompared with the blank group, fasting blood glucose of mice in the model group at weeks 1, 2, 3, and 4, blood glucose and area under the curve (AUC) at different time point of OGTT and ITT test, fasting serum insulin, and HOMA-IR increased (P<0.05, P<0.01); in the Morris water maze experiment, the escape latency increased from day 3 to day 5, and the number of crossing platforms, the percentage of target quadrant distance, and the percentage of target quadrant time decreased (P<0.05, P<0.01); the outer nuclear layer of the retina became sparse, thinner, and the number of ganglion cells decreases (P<0.01); the expression level of retinal glucose increased, while the expression levels of insulin, pIRS1/IRS1, PI3K/β-Actin, pAkt1/Akt1, and GLUT4 proteins decreased (P<0.01). Compared with the model group, fasting blood glucose at week 4, blood glucose at each time point of the OGTT and ITT tests AUC decreased (P<0.05, P<0.01), and fasting serum insulin and HOMA-IR decreased (P<0.05) in Dihuang Yinzi Decoction group; In the Morris water maze test, the escape latency shortened on day 4 and day 5, number of platform crossings, target quadrant distance as a proportion of total distance, and target quadrant movement time as a proportion of total time decreased (P<0.05, P<0.01); retinal pathological changes alleviated, and retinal thickness and ganglion cell number increased (P<0.01); retinal glucose content decreased, and retinal pIRS1/IRS1, PI3K/β-Actin, and GLUT4 protein expression elevated (P<0.05 or P<0.01). ConclusionsDihuang Yinzi Decoction can improve cognitive dysfunction of Alzheimer's disease, which may be related to regulating retinal insulin content and insulin signaling pathway.
3.Structure and function of neurovascular unit and its role in pathogenesis of cerebral ischemia injuries
Heyuan MA ; Qinqing LI ; Shifeng CHU ; Zhao ZHANG ; Wenbin HE
Chinese Journal of Pharmacology and Toxicology 2023;37(12):885-894
In recent years,increasing attention has been paid to the study on the pathogenesis of cerebral ischemia in terms of the overall structure and function of neurovascular unit(NVU),which has become one of the hot spots in the field of brain sciences and major brain diseases.This paper is intended to outline the roles of the four main NVU cells(neurons,astrocytes,microglia and cerebral microvascular endothelial cells)in brain function and pathogenesis of cerebral ischemia,which are closely related in structure,work together to maintain cerebral homeostasis in function,and play an important role in brain function and cerebral ischemic injuries.NVU injury leads to microvascular and blood brain barrier integrity impairment,neuronal cell death,glial reaction and immune cell infiltration,and even tissue injury and brain edema.This paper also aims to elucidate the roles of NVU structure and function in the pathogenesis of cerebral ischemia,and offer new ideas and strategies for the research related to drugs for prevention and treatment of cerebral ischemia based on NVU structure and function.
4.Study on Quality Standard of Cnidium monnieri Liniment
Xue HAN ; Jinmiao CHAI ; Qinqing LI ; Yonghui WANG
China Pharmacy 2018;29(9):1245-1248
OBJECTIVE:To formulate the quality standard of Cnidium monnieri liniment (called "liniment" for short)preliminarily. METHODS:The property of liniment was observed. TLC was used for qualitative identification of osthole in liniment;relative density,alcohol content and pH value were also determined. The osthole and imperatorin in liniment were analyzed qualitatively by HPLC. RESULTS:3 batch of samples were reddish brown liquid and fragrant smelling. In TLC of test sample,the same color fluorescent spots were found in corresponding position as chromatogram of control sample. The linear range of osthole and imperatorin were 0.101 2-0.910 8(r=0.999 6)and 0.006 2-0.124 4 mg/L(r=0.999 6). RSDs of precision tests were 1.38% and 0.79%(n=6). RSDs of stability tests were 0.33% and 0.41%(n=6). RSDs of reproducibility tests were 0.83% and 1.98%(n=6),respectively. Average recoveries rate were 98.73%(RSD=1.29%,n=6)and 99.25%(RSD=1.22%,n=6).Results of content determination showed that the content of osthole and imperatorin were 2.20-2.35 mg/mL and 0.310-0.340 mg/mL,respectively. CONCLUSIONS:Established method is simple,rapid,accurate and can be used for quality control of C. monnieri liniment.
5.Research progresses of breast background parenchymal enhancement of MRI
Qinqing LI ; Jun YANG ; Yingying DING ; Zhuolin LI
Chinese Journal of Medical Imaging Technology 2017;33(8):1273-1276
Breast background parenchymal enhancement (BPE) is a special form of breast dynamic contrast enhanced MRI.The diagnosis and research of breast diseases which shows BPE is becoming more and more important.The relationship between BPE and the risk factors of breast cancer is one of the focuses in breast MRI.In this review,the definition and typical manifestations of BPE,the relationship between BPE and fibroglandular tissue,and the influence factors of BPE in the breast MRI were reviewed.
6.The MRI diagnosis of the breast fibroadenoma with a washout type of the time signal intesity curve
Qinqing LI ; Jun YANG ; Yingying DING ; Zhuolin LI ; Yang LIU
Journal of Practical Radiology 2016;32(8):1205-1208
Objective To investigate the MRI findings of the breast fibroadenoma which has a washout type of time signal intensity curve (TIC)for the purpose of improving imaging diagnosis.Methods The MRI findings of 20 cases of the breast fibroadenoma with a washout TIC and 20 cases of breast carcinoma verified by histopathology were analyzed retrospectively.Morphological features,internal signal, ADC value and dynamic enhancement performance of the two groups were compared with each other.Results The shapes of the breast fibroadenomas were more commonly ovoid or round (18/20),and the margins were circumscribed(16/20),Most of the fibroadenomas were high intensity in T2 WI with the non-contrast enhanced separations (9/20).The average minimum ADC value was (1.412±0.332)×10-3 mm2/s,and higher than that of breast cancer (0.888 ±0.1 60)×10 -3 mm2/s with the significant difference (P <0.05).Enhancement scanning showed relatively homogeneous enhancement (16/20).The early enhancement ratio of the breast fibroadenoma was (1.694±0.628)×100% on average,and lower than that of breast cancer (1.849 ±0.430)× 100%.The difference was no statistical significance(P >0.05 ). Conclusion The breast fibroadenoma with washout TIC has a similar performance with the breast cancer in TIC and the early enhancement rate, however,the clear edge,higher T2 WI signal intensity,the non-contrast enhanced internal separations and higher ADC values are helpful to the diagnosis of breast fibroadenoma with washout TIC.
7.The application of manganese-enhanced MRI in stereotaxic techniques of rat visual nuclei
Jun YANG ; Qinqing LI ; Yingying DING ; Guangjun YANG ; Yu XIE ; Chan ZHU ; Chengde LIAO ; Zhuolin LI
Journal of Practical Radiology 2016;(2):295-298
Objective To explore the value of manganese-enhanced MRI in locating the rat visual nuclei.Methods The visual nuclei of thirty-six rats were located by 3 different ways including individual MEMRI locating (group A,n= 1 6),anatomical atlas locating (group B,n=1 6)and direct puncture by using the data obtained in MEMRI (group C,n=4).After unilateral intra-vitreal injection of MnCL2 (30 mmol/L×3 μL)in group A,the brain MRI was performed 24 h later.The location coordinate of lateral geniculate nucleus (LGN) and superior colliculus (SC)were recorded individually.The nuclei injections (3% fluorogold solution,1 μL)were performed by using different location coordinate in groups A and B.The rat’s retinas were examined under fluorescence microscope 5 days later,and the results were compared between the two groups.After brain nucleus puncture injection (30 mmol/L MnCL2 solution,0.5 μL),MRI was performed 1 h later in group C.Results The success rate was 93.8% (1 5/1 6)in group A,and 65.5% (10/1 6)in group B.The difference between groups was statistically significant (P<0.05).All the injection locations of C group were agreed with atlas.Conclusion MEMRI in the visual nucleus stereotactic can improve the accuracy of location.
8.Optimal dose research on manganese-enhanced MRI of rats optic nerve tracking
Jun YANG ; Qinqing LI ; Chengde LIAO ; Yingying DING ; Dafu ZHANG ; Yusen FENG
Journal of Practical Radiology 2015;(8):1370-1373
Objective To investigate the optimal concentration of manganese-enhanced MRI (MEMRI)in the visual pathway of experimental rats.Methods Sprague-Dawley rats were intravitreally injected with 3 μL of 10 - 100 mmol/L MnCl2 ,respectively. The contrast-to-noise ratio (CNR)of MEMRI for optic nerve(ON)and midbrain superior colliculus (SC)enhancement were measured at differ-ent concentrations of MnCl2 .Results The ON and SC were all clearly detected by MEMRI 24 h after unilateral intravitreal injected 10-100 mmol/L MnCl2 ,respectively.The CNR increased with the increasing concentration of MnCl2 from 10 to 50 mmol/L;But the CNR decreased from 50 to 100 mmol/L.The enhancement of superior colliculus were higher than optic nerve.Conclusion The optimal concentration of MnCl2 is 30 mmol/L(3 μL)through intravitreal injection for the rat visual pathway on 1.5T MEMRI.
9.CT features of multi-parasite infection in liver
Jun YANG ; Qinqing LI ; Yingying DING ; Chengde LIAO ; Guanshun WANG ; Conghui AI
Journal of Practical Radiology 2015;(7):1121-1124
Objective To discuss the CT manifestations of multi-parasite infection in liver to improve the diagnostic accuracy. Methods A total of 11 patients with ELISA-proved multi-parasite infection in liver were enrolled in this study.The plain and dynamic enhanced CT scans were performed.The imaging findings including the number,distribution,size,shape,density,enhancement and degree intratumaral features,cholangiectasis and abdominal lymphadenopathy were retrospectively analyzed.Results A single lesion of multi-parasite infection in liver was detected in 6 patients and multiple lesions were in other 5.The lesions in 8 patients were located in a single lobe of the liver,and involved in several hepatic lobes in other 3.The maximum diameter of the lesion ranged from 1.7 cm to 6.3 cm with an average diameter of 4.4 cm.Irregular lesions were found in 7 patients and round ones in shape were in other 4.Plain CT showed the lesions with low-intensity.All lesions were mild to moderate inhomogeneous enhancement on portal vein phase,presented honeycomb-like or separated enhancement with cholangiectasis (n=2)and abdominal lymphadenopathy (n=2).Conclusion The CT manifestations on portal vein phase in combination with clinical data are useful for the diagnosis of multi-parasite infection in liver.
10.Study on Quality Standard for Fufang Tianma Gouteng Orally Disintegrating Tablets
Qinqing LI ; Lei GUO ; Junlong ZHANG ; Jinmiao CHAI
Chinese Journal of Information on Traditional Chinese Medicine 2014;(2):85-87
Objective To establish the quality standard of Fufang Tianma Gouteng Orally Disintegrating Tablets. Methods Gastrodiae Rhizoma, Uncariae Ramulus Cum Uncis, Angelicae Sinensis Radix and Paeoniae Radix Alba in the preparation were identified by TLC, the content of gastrodin in gastrodia was determined by HPLC. Results The herbs of preparation could be identified by TLC without interference. Gastrodin showed a good linear relationship in the range of 0.191 2-1.147 2 μg (r=0.999 9). The average recovery was 97.72% (RSD=1.40%, n=6). Conclusion The methods are available with a good reproducibility, and can control the quality of the preparation effectively.

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