Role of estrogen in alleviating hemorrhagic shock-induced organ injury / 中国病理生理杂志

Estrogen has many biological activities and extensive clinical applications.Hemorrhagic shock-in-duced major organ dysfunction and injury,which are related to sex differences,play a triggering role in irreversible shock. The present article reviews the role of estrogen in alleviating hemorrhagic shock-induced organ injury by analyzing and sum-marizing the recent studies,thus expanding the clinical application of estrogen and providing a novel approach for treatment of severe hemorrhagic shock.

Aqueous extracts of Ocimum grasstimum inhibits lipopolysaccharide-induced interleukin-6 and interleukin-8 expression in airway epithelial cell BEAS-2B / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the antiinflammatory activities of aqueous extract of Occimum gratissmium (OGE) with emphasis on expression of proinflammatory cytokines in Lipopolysaccharide (LPS)-stimulated epithelial cell BEAS-2B.</p><p><b>METHODS</b>Effects of OGE on cell viability were determined by MTT assay. mRNA expression were analyzed by and reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR. Activation of kinase cascades was investigated by immunoblot. Intracellular reactive oxygen species (ROS) was analyzed by flow cytometry.</p><p><b>RESULTS</b>OGE (<200 μg/mL) treatment or pretreatment and following LPS exposure slightly affected viability of BEAS-2B cells. Increase of interleukin (IL)-6 and IL-8 and the elevated level of intracellular ROS in LPS-stimulated BEAS-2B cells were diminished by OGE pretreatment in a dose-dependent manner. OGE suppressed inflammatory response-associated mitogen-activated protein kinases (MAPKs) and Akt activation. Additionally, OGE pretreatment increased level of cellular inhibitor of κBα (IκBα) and inhibited nuclear translocation of nuclear factor kappa B (NF-κB).</p><p><b>CONCLUSION</b>These findings indicate that significant suppression of IL-6 and IL-8 expressions in LPS-stimulated BEAS-2B cells by OGE may be attributed to inhibiting activation of MAPKs and Akt and consequently suppressing nuclear translocation of NF-κB.</p>

Changes of erythrocyte rheology in rabbits with acute renal failure / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the change of erythrocyte theology in rabbits with acute renal failure (ARF).</p><p><b>METHODS</b>Thirty-eight healthy rabbits were randomly divided into control group (n = 8), model group (establishing ARF model via intramuscular injection 1% HgCl2, and divided into 12 h, 24 h, 48 h subgroups, all n = 10), the arterial blood sample was taken out through carotid artery at corresponding times after anesthetization with urethane, for detecting the indices of renal function and erythrocyte rheology.</p><p><b>RESULTS</b>The levels of urea and creatinine in plasma of model rabbits at 12 h, 24 h and 48 h were higher than those of control group, and there was a rise trend along with the time extension. The erythrocytes electrophoresis time at 12 h of model group was higher, the electrophoresis rate and migration rate of erythrocytes were lower compared with those of control group; the erythrocytes electrophoresis time at 24 h of model group was lower and the electrophoresis rate and migration rate were higher compared with those of model group at 12 h; and there were no statistical differences in erythrocytes electrophoresis indices between model group at 48 h and other groups. Meanwhile, there was a rise trend in erythrocyte sedimentation rate (ESR), K value of equation and emendation along with the time extension of ARF, but these indices only at 48 h of model group was lower significantly than that of control group. There were no statistical differences in aggregation index and deformability index of erythrocytes among groups.</p><p><b>CONCLUSION</b>During the process of ARF, the erythrocytes electrophoresis time lengthen and electrophoresis rate and migration rate decrease at early stage, and these indices gradually return to normal; the indices of ESR increase gradually.</p>

Inhibitory Effect of Melanoma Differentiation Associated Gene-7/Interleukin-24 on Invasion In Vitro of Human Melanoma Cancer Cells

The acquisition of metastasis potential is a critical point for malignant tumors. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a potential tumor suppress gene and frequently down-regulated in malignant tumors. It has been implicated that overexpression of MDA-7 led to proliferation inhibition in many types of human tumor. Invasion is an important process which is potential to promote tumor metastasis. However, the role and potential molecular mechanism of mda-7/IL-24 to inhibit the invasion of human melanoma cancer is not fully clear. In this report, we identified a solid role for mda-7/IL-24 in invasion inhibition of human melanoma cancer LiBr cells, including decreasing of adhesion and invasion in vitro, blocking cell cycle, down-regulating the expression of ICAM-1, MMP-2/9, CDK1, the phosphorylation of ERK and Akt, NF-kappaB and AP-1 transcription activity. Meanwhile, there was an increased expression of PTEN in mda-7/IL-24 over-expression LiBr cells. Our results demonstrated that mda-7/IL-24 is a potential invasion suppress gene, which inhibits the invasion of LiBr cells by the down-regulation of ICAM-1, MMP-2/9, PTEN, and CDK1 expression. The molecular pathways involved were the MAPK/ERK, PI3K-Akt, NF-kappaB, and AP-1. These findings suggest that mda-7/IL-24 may be used as a possible therapeutic strategy for human melanoma cancer.

Changes of blood viscosity and erythrocyte rheology in acute hypoxic hypoxia mices / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the changes of blood viscosity and erythrocyte rheology in mice after acute hypoxic hypoxia (AHH).</p><p><b>METHODS</b>Thirty-two Kui-ming mice were randomly divided into control group, AHH group (duplicating AHH model, and divided into 5 min, 8 min, 11 min subgroups), the blood sample was taken out from heart after neck dislocation at corresponding times, for detecting the blood viscosity and erythrocyte rheology indices.</p><p><b>RESULTS</b>Compared with control group, the whole blood viscosity at different shears, whole blood reduced viscosity, whole blood relative viscosity were lower and the erythrocytes aggregation index was higher in AHH 5 min group; the electrophoresis time was longer and the electrophoresis length, migration of erythrocyte were lower in AHH 8 min and AHH 11 min groups. The whole blood reduced viscosity, whole blood relative viscosity, erythrocytes aggregation index in AHH 8 min group were higher, and the erythrocyte deformability index was lower significantly than that of AHH 5 min group, respectively.</p><p><b>CONCLUSION</b>These data suggested that the AHH could induce the blood viscosity and electrophoresis ability.</p>

Involvement of protein kinase C in enhancement of vascular calcium sensitivity by blocking mesenteric lymph return in hemorrhagic shock rats / 生理学报

The aim of the present study was to investigate whether protein kinase C (PKC) was involved in the effect of mesenteric lymph duct ligation or mesenteric lymph drainage on vascular calcium sensitivity in hemorrhagic shock rats. Male Wistar rats were randomly divided into Sham, Shock (hemorrhagic shock), Shock+Ligation (mesenteric lymph duct ligation plus shock) and Shock+Drainage (mesenteric lymph drainage plus shock) groups. After being in shock (hypotension 40 mmHg) for 3 h, the tissue of superior mesenteric artery (SMA) was taken out for detecting the PKC expression and phospho-PKC (p-PKC) activity, and the vascular rings of SMA were prepared and used to measure the response to gradient calcium concentration for assaying the calcium sensitivity, the parameters of which including tension, maximum tension (E(max)) and negative logarithm of EC(50), called the pD(2). Other vascular rings from Shock+Ligation and Shock+Drainage groups were incubated with PKC regulator PMA or Staurosporine before the measurement of calcium sensitivity. The results showed that, PKC expression, p-PKC activity and calcium sensitivity of SMA in Shock group was significantly lower than that of Sham group, whereas the above-mentioned indexes were significantly elevated in Shock+Ligation and Shock+Drainage groups compared with those in Shock group. PKC agonist PMA enhanced the contractile activity of vascular rings to gradient calcium ions, and increased E(max) of SMA in Shock+Ligation and Shock+Drainage groups. On the contrary, PKC inhibitor Staurosporine significantly decreased the response to gradient calcium ions and E(max) of SMA in Shock+Ligation and Shock+Drainage groups. These results suggest that PKC plays a role in the improvement of vascular calcium sensitivity by blockade of mesenteric lymph return in hemorrhagic shock rats.

Reactivity to substance P of isolated lymphatics in hemorrhagic shock rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the change of lymphatic reactivity to substance P (SP) during the process of hemorrhagic shock (HS) with a technique of lymphatic perfusion in vitro in this study.</p><p><b>METHODS</b>Male Wistar rats were randomly divided into control group (surgical procedure only) and HS group (the rats in this group were further divided into five subgroups: shock 0 h, 0.5 h, 1 h, 2 h and 3 h groups after duplicating the HS model with method of bloodletting to mean arterial blood pressure was 40 mmHg through the femoral venous). Thoracic ducts were separated from HS rats at the corresponding time points in each group. A segment of thoracic duct was pressed and perfused in vitro at transmural pressure of 3 cm H2O, and then stimulated with gradient SP respectively. The end systolic diameter, end diastolic diameter, contraction frequency (CF) and passive diameter of isolated lymphatics were measured, while the contraction amplitude (CA), tonic index (TI) and fractional pump flow (FPF) were calculated, and the different values between pre- and post- administration of SP of CF, CA, TI and FPF were calculated and expressed as Delta CF, Delta TI, Delta CA and Delta FPF to further assess the reactivity of lymphatics.</p><p><b>RESULTS</b>After SP incubation, the Delta CF, Delta TI, Delta CA and Delta FPF of 0 h- and 0.5 h shocked lymphatics were significantly increased when compared with that of control group on one or several concentrations. The Delta CF (at 3 x 10(-7) mol/L of SP) and Delta TI (1 x 10(-7) mol/L) of 2 h- shocked lymphatics and the Delta CF (1 x 10(-7) mol/L, 3 x 10(-7) mol/L), Delta TI (1 x 10(-7) mol/L) and Delta CA (1 x 10(-7) mol/L) of 3 h- shocked lymphatics were all significantly reduced when compared with control group.</p><p><b>CONCLUSION</b>The reactivity of lymphatics to SP presented a biphasic change during the process of HS: increase in early phase and decline in later stage.</p>

Role of endotoxin translocation on mesenteric lymph reperfusion aggravating multiple organ injury in SMAO shock rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the role of mesenteric lymph reperfusion (MLR) aggravates multiple organs injury in superior mesenteric artery occlusion (SMAO) shock and its mechanism.</p><p><b>METHODS</b>Twenty four Wistar rats were randomly divided into 4 groups (n = 6): Sham group (only anesthetized and operated), MLR group rats performed 1 h occlusion of mesenteric lymph duct (MLD), then followed by 2 h of reperfusion, SMAO group (rats performed 1 h occlusion of superior mesenteric artery (SMA) and then followed by 2 h of reperfusion), SMAO + MLR group (rats performed 1 h occlusion of SMA and MLD and then followed by 2 h of reperfusion). The blood sample was taken out from abdominal aortic for plasma and the liver, kidney, myocardium, lung tissues in fixed position were prepared for making homogenate after reperfusion of 2 h respectively. And the levels of endotoxin (ET) in plasma and homogenates were determined with kinetic turbidimetric technique of tachypleus amebocyte lysate, the contents of lipopolysaccharide-binding protein (LBP), lipopolysaccharide receptor (CD14) and tumor necrosis factor-alpha (TNF-alpha) in homogenates were determined with enzyme-linked immunosorbent assay method.</p><p><b>RESULTS</b>The indices have no statistics difference between sham group and MLR group. The ET levels of the plasma and hepatic, renal, myocardial, pulmonary homogenates in SMAO and SMAO + MLR groups were significant higher than that of sham and MLR groups, and these indices in SMAO + MLR were increased significantly than those in SMAO group. The CD14, LBP and TNF-alpha contents of the hepatic, renal, myocardial and pulmonary homogenates in SMAO and SMAO + MLR groups were significant higher than those in sham and MLR groups, and these indices in SMAO+ MLR were higher than SMAO group significantly.</p><p><b>CONCLUSION</b>The mechanism of MLR aggravates multiple organs injury in SMAO shock may be associated with enterogenous ET through intestinal lymphatic pathway to translocate, activate the LBP/CD14 as endotoxin sensitizing system and promote inflammatory response.</p>

The effects of mesenteric lymph drainage on erythrocyte rheology in rats with hemorrhagic shock / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effects of mesenteric lymph drainage on erythrocyte rheology and blood viscosity in hemorrhagic shock rats.</p><p><b>METHODS</b>Wistar rats were randomly divided into sham-shock group, shock group (establishing hemorrhagic shock model), drainage group (establishing hemorrhagic shock model plus drainaging shock mesenteric lymph from hypotension 1 h). At 3 h of hypotension or corresponding time, blood samples were harvested from the abdominal aorta for determining the erythrocytic parameters, erythrocyte electrophoresis, erythrocyte sedimentation rate (ESR) and blood viscosity, and the erythrocytes aggregation index and erythrocyte deformability index were calculated.</p><p><b>RESULTS</b>Compared with the sham-shock group, the red cell contents, hematocrit (HCT), hemoglobin (Hb), mean corpuscular hemoglobin concentration (MCHC), erythrocyte electrophoretic rate and mobility, erythrocyte deformability index, whole blood viscosity, whole blood relative or reduced viscosity at low and high shear rates in shock group were observably lower, and mean corpuscular volume, electrophoretic time of erythrocyte, ESR, K value of equation and K value of emendation, erythrocytes aggregation index, plasma viscosity in shock group were increased markedly; the MCHC, erythrocyte electrophoretic rate and mobility, whole blood viscosity, whole blood relative viscosity at low and high shear rates in drainage group were reduced, and the red blood cell volume distribution width -SD (RDW-SD) was increased remarkably. At the same time, in drainage group, the HCT, RDW-SD, erythrocyte deformability index, whole blood viscosity and relative viscosity at low and high shear rates were higher, the ESR, K value of equation and K value of emendation, erythrocytes aggregation index, plasma viscosity were lower than that of shock group.</p><p><b>CONCLUSION</b>The results indicate that the mesenteric lymph drainage could improve the erythrocyte rheological behavior, as a result, improve the hemorrheological properties in hemorrhagic shock rats.</p>

Interference effects of lymph plasma on endotoxic shock in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the interference effects of lymph plasma on endotoxic shock and its mechanism.</p><p><b>METHODS</b>Sixty Wistar male rats were randomly divided into three groups: control group, model group and lymph plasma group. The endotoxic shock model of rats were duplicated by jugular intravenous injection with LPS (15 mg/kg), and after 15 minutes the normal lymph plasma was infused in lymph plasma group rats, which amount of lymph plasma was one fifteenth of whole blood volume. The effects of lymph plasma on the mean arterial pressure (MAP), microcirculation of mesentery near the ileum lower, the numbers of leukocytes adherent to the venular wall, the P-selectin and intercellular adhesion molecule-1 (ICAM-1) in plasma were observed.</p><p><b>RESULTS</b>The normal lymph plasma might be prevent from progressive decreased of MAP, depress the pathologic diameter constriction of mesenteric microvessels, reduce leukocytes adherent to the venular wall, improve blood flow condition of microcirculation, and decrease the level of P-selectin and ICAM-1 in plasma (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>A little of normal lymph plasma plays a positive interference effect on microcirculatory dysfunction and hypotension with endotoxic shock induced by LPS challenge. Those mechanisms may be concerned with decreasing the production of cell adhesion molecules.</p>

Nitric oxide modulates biphasic changes of isolated lymphatic contraction in hemorrhagic shock rats / 生理学报

The aim of the present study was to investigate the changes of lymphatic contraction after hemorrhagic shock in vitro and the underlying role of nitric oxide (NO). Rat thoracic duct segments were isolated at 0, 0.5, 1, 2 and 3 h after hemorrhagic shock. Using Pressure Myograph System, we determined contraction frequency (CF), end systolic diameter (ESD), end diastolic diameter (EDD) and passive diameter (PD) of isolated rat lymphatics under different transmural pressures (1, 3, 5, 7 and 9 cmH(2)O), then calculated contraction amplitude (CA), tonic index (TI) and fractional pump flow (FPF) of lymphatics. The results showed that in several transmural pressures, lymphatic CF, TI and FPF were significantly higher in shock 0 h and shock 0.5 h groups than those in control group (sham operation group). With the development of shock, lymphatic CF, TI and FPF decreased significantly in shock 2 h and shock 3 h groups compared with those in control group. We further discovered the role of NO in the changes of lymphatic contraction after hemorrhagic shock. Under 3 cmH(2)O transmural pressure, the changes of lymphatic contraction in shock 0.5 h and shock 2 h groups were analyzed following the incubation with several NO-related drugs alone or in combination. And the results showed that NO donor L-Arg reduced CF, TI and FPF in shock 0.5 h group to the control levels, while soluble guanylate cyclase inhibitor ODQ suppressed the effect of L-Arg. Moreover, NOS inhibitor L-NAME elevated the CF, TI and FPF of 2 h shock lymphatics to the control levels, while phosphodiesterase inhibitor aminophylline (AP) suppressed the effect of L-NAME. These results suggest that the lymphatic contractile activity exhibits a biphasic change during hemorrhagic shock, increasing in early phase and declining in later stage. And NO plays a major regulating role in the biphasic change of lymphatic contraction in hemorrhagic shock rats via cGMP pathway.

Effect of mesenteric lymph duct ligation on erythrocyte rheology in acute hemorrhagic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effects of mesenteric lymph duct (MLD) ligation on erythrocyte rheology in acute hemorrhagic rats.</p><p><b>METHODS</b>Twenty male Wistar rats were randomly divided into hemorrhage group and ligation group (n = 10). Blood (one fourth of body whole blood volume) was withdrawn through right common carotid arteries after rats were anesthetized. In ligation group, the MLD was ligated after hemorrhage, and only threading under the MLD in hemorrhage group. The survival situation at 24 h was recorded. After 24 h, survival rats were anesthetized again, blood sample was withdrawn through left common carotid artery rapidly. And the erythrocyte sedimentation rate (ESR), electrophoresis of erythrocytes, hematocrit (Hct) were determined in blood samples of before and after hemorrhage, the erythrocytes aggregation and deformability indices were calculated.</p><p><b>RESULTS</b>It showed that the ligation group survival (9 rats alive) was slightly better than that in hemorrhage group (6 rats alive). The results of erythrocyte rheology indices showed that the ESR, K value of equation, K value of emendation and electrophoresis time in hemorrhage group and ligation group were higher or longer than those before hemorrhage, the erythrocyte deformability was reduced significantly, respectively. And the erythrocytes aggregation index in hemorrhage group was increased, the electrophoresis length and migration of erythrocyte in hemorrhage group were lower than those before hemorrhage, respectively. But compared with hemorrhage group, the ESR, K value of equation, K value of emendation, erythrocytes aggregation index and electrophoresis time in ligation group were lower, the electrophoresis lenght, migration and deformability of erythrocyte were increased significantly.</p><p><b>CONCLUSION</b>The results indicate that the higher erythrocyte aggregation ability, lower electrophoresis function and deformability are caused by acute hemorrhage in rats, and the MLD ligation can improve the abnormal erythrocyte rheology.</p>

Expression of cannabinoid receptor 2 in squamous cell carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of cannabinoid receptor 2 (CB2) in normal human skin and squamous cell carcinoma and analyze its relation with the tumorigenesis and development of squamous cell carcinoma.</p><p><b>METHODS</b>The expression of CB2 protein and mRNA levels were detected in normal human skin and squamous cell carcinoma using immunohistochemical staining and RT-PCR.</p><p><b>RESULTS</b>Both the normal skin and squamous cell carcinoma expressed CB2, which was localized mainly in the basal cell layer and prickle cell layer in human skin with low expressions in the subcutaneous tissue. The expression intensity of CB2 differed significantly between squamous cell carcinoma and normal human skin (P<0.05).</p><p><b>CONCLUSION</b>Squamous cell carcinoma over-expresses CB2 at both the protein and mRNA levels. High expression of CB2 in squamous cell carcinoma suggests an important role of CB2 in the tumorigenesis and development of squamous cell carcinoma.</p>

Effect of intestinal lymphatic pathway on free radical and inflammatory mediator of myocardium in shock rats / 中国应用生理学杂志

<p><b>AIM</b>To observe the effect of mesenteric lymph duct ligation on free radical and inflammatory mediator of myocardium with severe hemorrhagic shock in rats at different period, and explore the effect of intestinal lymphatic pathway on myocardium injury pathogenesis in shock rats.</p><p><b>METHODS</b>78 male Wistar rats were divided into the sham group, shock group and ligation group. The model of serious hemorrhagic shock was established in shock group, ligation group, and mesenteric lymph was blocked by ligating mesenteric lymph duct in ligation group after resuscitate. All rats were executed and taken out heart making for homogenate of 10 percent to determine the MDA, SOD, tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), myeloperoxidase (MPO), NO and NOS at after shock 90 min, after transfusion and resuscitate 0 h, 1 h, 3 h, 6 h, 12 h and 24 h etc. different times, and the expression of inducible nitric oxide synthase (iNOS) mRNA in myocardium was detected by RT-PCR.</p><p><b>RESULTS</b>The contents of MDA, TNFalpha, IL-6, MPO, NO, NOS and iNOS expression in myocardium of shock group were rising after transfusion and resuscitate, and that was higher level at 3 h to 12 h, and that was significantly higher than sham group, the activity of SOD was significantly lower than sham group. The contents of MDA, TNFalpha, IL-6, MPO, NO, NOS and iNOS expression in myocardium of ligation group were significantly lower than that of shock group at sameness points, and the SOD activity was higher.</p><p><b>CONCLUSION</b>The mesenteric lymph duct ligation and blocking mesenteric lymph could reduce the PMN detaining, decrease the discharging of TNFa and IL-6, reduce the NO and expression of iNOS mRNA, and reduce the releasing of free radical and consuming of SOD.</p>

Experiment Design and Comment in Pathophysiololgy Teaching / 中华医学教育探索杂志

We have carried out experiment design and comment,and students write the reports of experiment design in patho- physilolgy teaching from the aspects of basic process of experiment research and basic factors,principle and meaning of experi- ment design.By way of the teaching reform,the major position of students in studying is established,students' ability to study in- dependently and acquire knowledge actively are well cultivated,their comprehensive quality are enhanced and the teachers con- struction is also promoted.