1.Cardiac-targeted liposomes alleviate myocardial ischemia-reperfusion injury by promoting inflammation resolution
Guangrui ZHU ; Xueyi WENG ; Weiyan LI ; Yanan SONG ; Zheyong HUANG
Chinese Journal of Clinical Medicine 2026;33(2):240-249
Objective To explore the pro-inflammation resolution and protective effects of reactive oxygen species (ROS)-responsive liposomes modified with a cardiac-targeted peptide and loaded with resolvin D1 (RvD1, C-LP-RvD1) on myocardial ischemia-reperfusion (MI/R) injury. Methods The C-LP-RvD1 nanoliposomes were constructed, characterized physically and chemically, and evaluated for in vitro release. Non-targeting peptide-modified drug-loaded liposomes (LP-RvD1) were served as controls. Apoptotic adult mouse cardiomyocytes (AMCMs) were used to verify in vitro targeted binding capacity of C-LP-RvD1. In MI/R mice models, the in vivo distribution and cardiac enrichment of C-LP-RvD1 were assessed. Levels of specialized pro-resolving mediator (SPM) and inflammatory factors in cardiac tissue homogenates and cell culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Cardiac function and fibrosis remodeling were evaluated via echocardiography and Masson staining four weeks after treatment. Biosafety was evaluated in healthy mice injected by C-LP-RvD1. Results The C-LP-RvD1 exhibited good nanoscale uniformity and stability, with ROS-triggered accelerated release characteristics. In vitro experiments showed that C-LP-RvD1 had higher binding capacity to apoptotic AMCMs than LP-RvD1, with significantly higher SPM levels (P<0.01) and lower inflammatory factor levels (P<0.05). In vivo experiments indicated enhanced cardiac enrichment of C-LP-RvD1 in MI/R injured hearts, with higher local myocardial SPM levels and lower inflammatory factor levels compared to LP-RvD1 (P<0.05). Four weeks after treatment, compared with LP-RvD1, the C-LP-RvD1 mice group showed improved cardiac function indicators and reduced ventricular fibrosis remodeling ratio (P<0.05). Safety evaluation revealed no significant systemic inflammation, immunogenicity, or coagulation abnormalities in healthy mice, with liver and kidney function and major organ histology showing no notable damage. Conclusions C-LP-RvD1 improves effective delivery of RvD1 to MI/R injured hearts through injury-targeted enrichment and ROS-responsive release, promoting inflammation resolution and suppressing excessive inflammation, thereby improving cardiac function and reducing adverse remodeling, with favorable biosafety.
2.Effect of vitamin B6 on vascular endothelial injury of atherosclerosis mice and its mechanism
Moli ZHU ; Yifei LI ; Zhenzhen LI ; Haiyan ZHAO ; Yanhua LIU ; Yue QIU ; Guangrui WAN ; Peng LI
Journal of Xinxiang Medical College 2024;41(1):1-7
Objective To investigate the effect of vitamin B6(VB6)on vascular endothelial injury of atherosclerosis(AS)mice and its mechanism.Methods Thirty-six ApoE-/-mice were randomly divided into control group,AS group,VB6 group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group,with 6 mice in each group.The mice in the AS group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group were fed with high-fat diet for 12 weeks to establish the AS model;the mice in the control group and VB6 group were given regular diet and normal drinking water for 12 weeks.After 12 weeks,the mice in the control group were given conventional diet and the same volume of physiological saline as the VB6 group daily by gavage;the mice in the VB6 group were given routine diet and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+LiCl group were given high-fat diet continuously and LiCl(1 mg·kg-1)by gavage daily;the mice in the AS+VB6 group were given high-fat diet continuously and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+VB6+LiCl group were given high-fat diet continuously and VB6(50 mg·kg-1),LiCl(1 mg·kg-1)by gavage daily;all mice were intervened for 4 weeks.After intervention,the serum nitric oxide(NO),malondialdehyde(MD A)levels and superoxide dismutase(SOD)activity of mice in each group were measured by enzyme linked immunosorbent assay.Hematoxylin-eosin staining was used to observe the morphology of thoracic aortic tissue of mice in each group and the percentage of AS plaque area to total vascular area was calculated.The vasodilatation rate of thoracic aorta was detected by isolated vascular ring experiment.The expression of sodium/hydrogen exchanger 1(NHE1)protein in thoracic aorta was detected by immunohistochemistry.Results Compared with the control group,the NO level and SOD activity in the serum of mice in the AS group decreased,while the MDA level increased(P<0.05);there was no significant difference in the NO,MDA levels and SOD activity in the serum of mice between the VB6 group and the control group(P>0.05).Compared with the AS group,the serum NO level and SOD activity of mice in the AS+VB6 group increased,while the MDA level decreased(P<0.05);there was no significant difference in serum NO,MDA levels and SOD activity of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P>0.05).Compared with the AS+VB6 group,the serum NO level and SOD activity of mice in the AS+VB6+LiCl group decreased,while the MDA level increased(P<0.05).The percentage of AS plaque area to total vascular area of mice in the AS group was significantly higher than that in the control group(P<0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice among the VB6 group and the control group(P<0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6 group was significantly lower than that in the AS group(P<0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P<0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P<0.05).In the control group,the vascular endothelium of mice was smooth with orderly arrangement of cells;in the AS group,AS+LiCl group and AS+VB6+LiCl group,the tissue structure of vascular of mice was disordered and the vascular endothelium was rough;in the VB6 group and AS+VB6 group,the vascular wall structure of mice was normal,the vascular endothelium was smooth,and the cells were arranged orderly.The vasodilatation rate of thoracic aorta of mice induced by acetylcholine(Ach)in the AS group was significantly lower than that in the control group(P<0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between the VB6 group and the control group(P>0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6 group was significantly lower than that in the AS group(P<0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between AS+LiCl group,AS+VB6+LiCl group and AS group(P>0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P<0.05).There was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by sodium nitroprusside among the six groups(P>0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS group was significantly higher than that in the control group(P<0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice between the VB6 group and the control group(P>0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6 group was significantly lower than that in the AS group(P<0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice among the AS+LiCl group,AS+VB6+LiCl group and the AS group(P>0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P<0.05).Conclusion VB6 can improve vascular endothelial injury in AS mice via inhibiting the expression of NHE1 protein.
3.Investigation Report of Chinese Medicinal Materials Artificial Planting in Lanzhou City
Renyuan ZHU ; Aihua DING ; Yun LI ; Guoyu QIU ; Hui DING ; Yan LI ; Caixia ZHANG ; Guangrui LIU
China Pharmacy 2019;30(11):1535-1540
OBJECTIVE: To provide reference for promoting large-scale, standardized and high-quality planting of Chinese medicinal materials. METHODS: Through the communication by phone with the agriculture bureau of each district and county, the contact with the relevant township government and the field visit investigation during Jun. 2013-Dec. 2018 by Lanzhou institute for food and drug control, variety, area, yield and output value, cultivation techniques and processing methods of Chinese medicinal materials in the planting area of Lanzhou were investigated and statistically analyzed. The advantages and problems were analyzed, and reasonable suggestions for planting Chinese medicinal materials were put forward. RESULTS & CONCLUSIONS: In 2018, artificial planting of Chinese medicinal materials in lanzhou has a certain scale, with 21 artificial planting varieties, a total planting area of about 510 000 mu, an annual output of 170 000 tons, an annual production value of over 1.7 billion yuan. Cultivation techniques mainly include seedling transplanting, mulching or direct seeding, while drying is the main processing method. Artificial planting of Chinese medicinal materials in Lanzhou has a certain scale and prominent characteristic varieties; authenticity is guaranteed, and the combination of Chinese medicinal materials planting and tourism drives economic development. However, there are still some problems, such as a certain distance from the development of industrialization, variety degradation, backward basic research, serious natural disasters. It is suggested to strengthen its propaganda and expand its advantages, at the same time, enhance government support, develop and construct planting bases of Chinese medicinal materials, strengthen the awareness of good agricultural practice (GAP), strengthen scientific research strengeh, explore breeding techniques of fine varieties of Chinese medicinal materials, develop insurance of Chinese medicinal materials, and guarantee the development of planting industry so as to promote large-scale, standardized and high-quality planting of Chinese medicinal materials.
4.Effect ofRong-ShuanCapsule on Rodent Tolerance against Cerebral Ischemia, Hypoxia and Cerebral Reserve Capacity
Li XU ; Wenting SONG ; Jianxun REN ; Guangrui WANG ; Sheng ZHU ; Mingjiang YAO ; Jianxun LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(7):1386-1391
This study was aimed to observe the effect ofRong-Shuan (RS) capsule on rodent tolerance against cerebral ischemia, hypoxia and cerebral reserve capacity, which was related to promote blood circulation and remove blood stasis. Acute cerebral ischemia and anoxia models were established by permanent left carotid artery ligation on C57 BL/6 mice and hypoxia inhalation (O2?N2 = 8?92) for 15 min. Duodenal administration of RS capsule at different doses (100, 200 or 400 mg·kg-1) or saline were given 10 min after ischemia onset. The local brain blood circulation changes and neurobehavioral function were evaluated 24 h after ischemia onset. SD rats were given RS capsule at different doses (75, 150, 300 mg·kg-1) or saline. The effect of RS capsule on improvement of microcirculation disturbance induced by high molecular dextran was observed. The results showed that compared with the sham operation group, the brain blood circulation in the model group was significantly decreased; the cerebral infarction area increased; and the behavioral score after cerebral hypoxia was significantly increased (P < 0.05, orP < 0.01). Meanwhile, after the injection of high molecular dextran among rats in the model group, the cerebral leptomeninx microcirculation was obviously slowed down at 3 timepoints, which were 10, 20 and 30 min. Compared with the model group, RS capsule (400 mg·kg-1) can significantly increase the local blood circulation in the brain of mice, improve behavioral disturbance, reduce cerebral ischemia area (P< 0.05, orP < 0.01). RS capsule can also improve blood flow velocity and flow pattern in cerebral leptomeninx microcirculation disturbance induced by high molecular dextran at different timepoints (P < 0.05, orP < 0.01). It was concluded that RS capsule can increase the tolerance against cerebral ischemia, hypoxia and cerebral reserve capacity in order to protect the neural tissues to promote neuronal recovery.
5.Measuring the volume of insula in healthy Chinese adults of the Han nationality on the high-resolution MRI
Guangrui QI ; Nan CHEN ; Yulin GUO ; Yanbo LAI ; Xing WANG ; Rui GONG ; Kai ZHU ; Dan ZHAO ; Kuncheng LI ; Yan ZHUO ; Lin CHEN
Chinese Journal of Radiology 2010;44(6):585-588
Objective To explore the normal range of the insula volume of Chinese adults of the Han nationality and its relationship with age, which provide morphological data for the construction of database for Chinese Standard Brain.Methods This is a clinical multi-center study.One thousand Chinese healthy volunteers (age range = 18 to 70) recruited from 16 hospitals were divided into 5 groups, i.e.,Group A ( age range = 18 to 30), B ( age range = 31 to 40 ), C ( age range = 41 to 50 ), D ( age range =51 to 60), and E (age range =61 to 70).Each group contained 100 males and 100 females.All of the volunteers were scanned by MR using T1 weighted three-dimensional magnetization prepared rapid acquisition gradient echo sequence.After three dimension data reconstruction, the volumes of bilateral insula were manually measured.The volume of bilateral insula were compared by paired sample t test.The insula volumes were compared between male and female by independent sample t test, and the differences among 5 age groups were compared by one-way ANNOVA.The relationship between the volumes of insula and age,sex or cerebral volume were analyzed using bivariate correlation, respectively.Results The left snd right side volume of insula before standarized were (7764±1165) and (7387±1128) mm3 respectively, after standarized were (8413±1201 ) and (7871±1140) mm3 respectively.The left insula volume were significant larger than that of right(t = - 10.565, - 16.014,P <0.01 ).The left and fight volume of insula were (8146±1181 ) and (7735±1113) mm3 for male, and (7393±1022) mm3 and (7050±1038) mm3for female.The left and right insula volumes for male were larger than the female's(t = 10.934,9.945 ,P <0.01 ).The left and right insula volume of male after standarized were (8779±1230 ) and (8224±1081 )mm3, female were (8043±1054) and (7515±1091 ) mm3 ,the left and right insula volume of male were larger than the female's ( t = 4.858,4.632, P < 0.01 ).The left insula volumes among Group A, B, C, D,E before standarized were ( 8268±1221 ), ( 8067±1107 ), ( 7869±1109), ( 7603±1111 ), ( 6997±934 )mm3 respectively,the right were (8028±1156), (7636±1075), (7294±986), (7249±1068), (6717±916) mm3 respectively, there were significant differences among 5 groups between left and right insula volume(F= -0.361,-0.337,P <0.01 ).The left insula volume of A,B,C,D,E after standarized were ( 9093±1105 ), ( 8679±965 ), ( 8810±1136), ( 8202±980), ( 7273±940 )mm3, the right were ( 8694±1005), (8136±1100), (8034±910), (7496±990), (6989±932) mm3, there were significant differences among 5 groups between left and right insula volume(F = -0.490, -0.512,P < 0.01 ).There was significant negative correlation between the volume and age ( before standarizded:r = -0.361, -0.337, after standardized r = -0.490, -0.512, P<0.05).Before and after standardized, there was significant correlation between the volume of right and left insula and cerebral volume ( r = 0.470,0.459, P < 0.05 ).Before and after standardized, there was significant correlation between the volume of right and left insula and weight( r = 0.141, 0.092, P < 0.05 ).Conclusions 1.5 T MR scanner has high resolution, for distinguishing the white matter from the gray matter, and provide morphological data of insula for the construction of database for Chinese Standard Brain.

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