1.Change and Significance of Neutrophil Elastase (NE) and Matrix Metalloproteinase-9 (MMP-9) in Sepsis.
Min YU ; Xianzhe LIU ; Qun DENG
Journal of Medical Research 2006;0(03):-
Objective To investigate the change of neutrophil elastase and matrix metalloproteinase-9 in sepsis and determine significance in the early diagnosis and prognosis of multiple organ dysfunction syndrome.Methods The plasma levels of neutrophil elastase and matrix metalloproteinase-9 in 28 ICU patients with sepsis were examined by immunofluorescence.Results Compared with control group,the levels of NE and MMP-9 were significantly higher on the day of the diagnosis of sepsis(P
2.Observation of extracellular matrix damage in the kidney of rats with multiple organ dysfunction syndrome
Yurong YUAN ; Lin TENG ; Min YU ; Xianzhe LIU
Chinese Journal of Emergency Medicine 2012;21(8):819-824
ObjectiveTo determine the levels of type Ⅳ collagen and matrix metalloproteinase-9 ( MMP-9 ) in the serum and kidney of rats with the multiple organ dysfunction syndrome ( MODS ) and investigate the mechanism of extracellular matrix damage in renal failure of MODS.MethodsForty adult male Sprague- Dawley (SD) rats were randomly (ramdom number) divided into two groups,namely the normal control group ( n =8 ) and the MODS model group ( n =32 ).The rats of model group were further divided into four sub-groups as per different intervals,6 h,12 h,24 h and 48 h,after modeling (n =8 in each).The animal models of MODS were established by two hits,the left eyeball of each model rat was removed to bleed to 2 ml bloocd/100 g body weight and lipopolysaccharide ( LPS,5 mg/kg) was injected into intraperitoneal cavity of model rats four hours later. The same volume of saline instead was injected intraperitoneally into rats of control group.All rats were sacrificed at different intervals.Creatinine (Cr)and blood urea nitrogen (BUN) were determined by using a Hitachi Automatic Biochemical Analyzer.The histological changes in renal tissue were observed under light microscope and transmission electronic microscope.The levels of serum type Ⅳ collagen and MMP - 9 protein were measured by using enzyme linked immunosorbent assay (ELISA).Type Ⅳ collagen and MMP- 9 protein levels in renal tissue were detected by western blot.One - way ANOVA was used for comparison among multiple groups.Results Compared with the control group,Cr and BUN were significantly higher in MODS group ( P <0.05 ).There were no histopathological changes in kidney of rats in control group,and the renal injury was serious in rats with MODS.The remarkable edema of basement membrane and defect of collagen fibers in renal tissue were observed in MODS group.Compared with the control group,the levels of MMP-9 in serum increased 6-48 hours after modeling and peaking at interval of 12 hours after modeling ( P < 0.05 ).The protein levels of type Ⅳ collagen increased not significantly in 6 h group and 12 h group in comparison with control group (P > 0.05 ),while those in 24 h group and 48 h group significantly increased ( P < 0.01 ).The levels of MMP -9 in renal tissue of rats with MODS increased in 6 h group and 12 h group (P<0.05),peaked in 24 h group ( P < 0.05 ),and decreased in 48 hours.However,the level of Ⅳ collagen in serum of rats with MODS decreased significantly 6-48 hours after modeling (P < 0.05 ) Conclusions The injury of extracellular matrix is an important factor to the kidney damage in MODS and it may he used for early diagnose and as a treatment target for kidney injury in MODS.
3.TLR4 expression in the kidney of rats with multiple organ dysfunction syndrome
Lin TENG ; Min YU ; Junming LI ; Xianzhe LIU
Chinese Journal of Emergency Medicine 2011;20(12):1300-1305
Objective To determine the level of toll-like receptor4 (TLR4) in the kidney of rats with the Multiple Organ Dysfunction Syndrome (MODS),and to investigate the early phase of kidney damage in MODS.Methods The experiment was done at experimental center of medical college of Three Gorges University.Forty Adult male Sprague-Dawley (SD) rats were randomly (random number) divided into two groups,namely the normal control group and the MODS model group.The rats of model group were further divided into four sub-groups as per different intervals (6 h,12 h,24 h and 48 h),and there were 8 rats in each groups.The animal models of MODS were established by two hits,the left eyeball of each model rat was removed to bleed to 2 mL/100 g,and four hours later,Lipopolysaccharide ( LPS,5 mg/kg) was injected into intraperitoneal cavity of model rats.The same volume of saline was injected intraperitoneally into rats of control group.All rats were sacrificed at various intervals.The histological changes in the kidney tissue were observed by naked eye and under light microscope.The lever of TLR4 proteins in serum and kidney tissue were detected by using flow cytometry (FCM).One-way ANOVA was used for comparison among multiple groups.Results (1) There were no histopatholagical changes in kidney of rats in control group,and the kidney injury was serious in rats with MODS.(2) Compared with the rots of control group,the level of TLR4 in kidney tissue of rats with MODS increased at 6 hours and reached peak 12 hours later ( P < 0.01 ),and then decreased 24 hours ( P < 0.01 ).There was no significant difference in levd of TLR4 between two groups 6 and 48 hours.Compared with the rats of control group,the level of TLR4 in peripheral blood leucocyte of rats with MODS increased significantly 6 ~ 48 hours after LPS ( P < 0.01 ).The concentrations of serum and kidney tissue TLR4 proteins were positively correlated with each other ( r =0.893,P < 0.05 ).Conclusions The level of TLR4 markedly increased in the kidney tissue at early stage of MODS,and the TLR4 may play an important role in the pathogenesis of kidney injury in MODS.
4.Significance of thrombomodulin and matrix metalloproteinase-9 in sepsis and multiple organ dysfunction syndrome
Min YU ; Xianzhe LIU ; Qun DENG ; Min QIAN ; Xinli ZHANG
Chinese Journal of Emergency Medicine 2006;0(06):-
Objective To investigate the changes of thrombomodulin and matrix metalloproteinase-9 in sepsis and determine their significance in the early diagnosis and prognosis of multiple organ dysfunction syndrome. Methods The plasma levels of thrombomodulin and matrix metalloproteinase-9 in 32 ICU patients with sepsis were measured by immunofluorescence. Results Compared with control group,the levels of TM and MMP-9 were significantly higher on the day of the diagnosis of sepsis(P
5.Change of matrix metalloproteinase-9 in rats with multiple organ dysfunction syndrome
Min YU ; Guanlan LI ; Xianzhe LIU ; Min QIAN ; Xinli ZHANG ; Yuqi WU ; En LV ; Changyun GUO
Chinese Journal of Emergency Medicine 2009;18(2):165-169
Objective To investigate the changes in the serum MMP-9 (matrix metalloproteinase-9) and the expressions of MMP-9 in lung, kidney and intestine in rats with multiple organ dysfunction syndrome (MODS) and confirm extracellular matrix injuries being the mechanism in MODS in order to propose a novel theoretical basis for cfinical treatment of MODS. Method Forty wister rats were randomly divided into two groups: control group (n=8) and MODS model group (n=32). The rats of model group were further divided into four subgroups ac-cordingto the time elapsed after modelling: 12 h (n=8), 24 h(n=8) ,48 h(n=8) and 72 h (n=8), and were modelled by celiac injection of mixed liquid of zymosan-paraffin (4 mL/100 g) after blood loss (1mL/100 g) by extirpating their left eyes. Blood,lung, kidney and intestine were sampled 12,24,48 and 72 hours after models were established. The histological changes in the lung, kidney and intestine of the rats were observed by light mi-croscope. The serum MMP-9 were measured by enzyme-linked immunosorbent assay (ELISA). The immunohisto-chemistry was used to observe the expression of MMP-9 in lung,kidney and intestine during different phases of MODS. The data were processed by one-way ANOVA and Bivariate analysis. Results Compared with control group, the organs were injured by congestion, edema and inflammatory cells infiltration to a certain extent in model groups. The serum MMP-9 increased markedly 12 hours after modelling (P<0.01 ) and peaked 48 hours later. The expressions of MMP-9 in lung, kidney and small intestine significantly increased from 12 h to 72 h after mod-elling (P<0.01 or 0.05). Conclusions The MMP-9 increased both in serum and tissue are closely associated with the pathological process of MODS. The mechanism of organ damage probably attributes to the damage of extra-celluar matrix and tissue construction.
6.Immune cell membrane-based biomimetic nanomedicine for treating cancer metastasis.
Lingling ZHU ; Xianzhe YU ; Ting CAO ; Hanyu DENG ; Xiaojun TANG ; Qing LIN ; Qinghua ZHOU
Acta Pharmaceutica Sinica B 2023;13(6):2464-2482
Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.