LSD1: an emerging face in altering the tumor microenvironment and enhancing immune checkpoint therapy.

Dysregulation of various cells in the tumor microenvironment (TME) causes immunosuppressive functions and aggressive tumor growth. In combination with immune checkpoint blockade (ICB), epigenetic modification-targeted drugs are emerging as attractive cancer treatments. Lysine-specific demethylase 1 (LSD1) is a protein that modifies histone and non-histone proteins and is known to influence a wide variety of physiological processes. The dysfunction of LSD1 contributes to poor prognosis, poor patient survival, drug resistance, immunosuppression, etc., making it a potential epigenetic target for cancer therapy. This review examines how LSD1 modulates different cell behavior in TME and emphasizes the potential use of LSD1 inhibitors in combination with ICB therapy for future cancer research studies.

Cycloartane triterpenes from Beesia calthaefolia and their anticomplement structure-activity relationship study.

Fifteen cycloartane triterpenes were isolated from Beesia calthaefolia and among them one was new cycloartane triterpenoid. The structure of new compound was determined by the application of spectroscopic analyses and chemical methods. The fifteen compounds were evaluated for their anticomplement activity by classic pathway. The structure-activity relationship analysis indicated that the configurations of 12-OH is preferable to be α than ß, and 18-OH can decrease while 15-OH can increase the anticomplement activity, but saponin with both 15-OH and 18-OH lost most of its activity. The glycosyl moiety of most isolated cycloartane triterpenes is xylosyl. When xylosyl was substituted by glucosyl or galactosyl, their anticomplement activities were decreased or increased, respectively. Further structure-activity relationship (SAR) studies must be carried out to achieve general conclusions regarding the effect of further functionalizations on the anticomplement saponins.

Early Biomarkers in 1H Nuclear Magnetic Resonance Spectroscopy of Striatal Pathological Mechanisms after Acute Carbon Monoxide Poisoning in Rats.

OBJECTIVE: In vivo Proton Magnetic Resonance Spectroscopy (1H-MRS) can be used to evaluate the levels of specific neurochemical biomarkers of pathological mechanisms in the brain. METHODS: We conducted T2-Weighted Magnetic Resonance Imaging (MRI) and 1H-MRS with a 3.0-Tesla animal MRI system to investigate the early microstructural and metabolic profiles in vivo in the striatum of rats following carbon monoxide (CO) poisoning. RESULTS: Compared to baseline, we found significant cortical surface deformation, cerebral edema changes, which were indicated by the unclear gray/white matter border, and lateral ventricular volume changes in the brain. A significant reduction in the metabolite to total creatine (Cr) ratios of N-acetylaspartate (NAA) was observed as early as 1 h after the last CO administration, while the lactate (Lac) levels increased marginally. Both the Lac/Cr and NAA/Cr ratios leveled off at 6 h and showed no subsequent significant changes. In addition, compared to the control, the choline (Cho)/Cr ratio was slightly reduced in the early stages and significantly increased after 6 h. In addition, a pathological examination revealed mild cerebral edema on cessation of the insult and more severe cerebral injury after additional CO poisoning. CONCLUSION: The present study demonstrated that 1H-MRS of the brain identified early metabolic changes after CO poisoning. Notably, the relationship between the increased Cho/Cr ratio in the striatum and delayed neuropsychologic sequelae requires further research.

Mesoderm is committed to hemato-endothelial and cardiac lineages in human embryoid bodies by sequential exposure to cytokines.

Human embryonic stem (hES) cells can differentiate into cells of the three germ layers in vitro and serve as a powerful resource to study mechanisms involved in cell fate decisions. However, it is difficult to promote the directed and efficient differentiation of hES cells toward a specific lineage. Here we establish a stepwise strategy for generating hemato-endothelial and cardiac precursors from hES cells in single culture conditions. The efficiency of committing hES cells to three cell lineages was significantly higher with our approach than with exposure to single or multiple cytokines. Efficiency was determined using quantitative analysis by gene expression, flow cytometry, and colony assays. Several cytokines were sufficient to drive the efficient differentiation of hES cells into specific lineages. Each of these factors appeared to regulate specific steps of differentiation: BMP4 promoted the efficient formation of mesoderm; bFGF induced the differentiation of these mesodermal precursors to the hemangioblast fate; VEGF and TPO were required for the production of committed hematopoietic progenitors. This stepwise control of differentiation in vitro leads to a high frequency of hemato-endothelial and cardiac precursors derived from hES cells and offers a unique model for studying the molecular and cellular events that regulate hematopoiesis and cardiogenesis.

[The protective effect of chlorophyllin against oxidative damage and its mechanism].

OBJECTIVE: To investigate whether chlorophyllin could protect human umbilical vein endothelial cell (HUVEC) against oxidative damage by inducing the expression of heme oxygenase-1 (HO-1) and to explore the underlying mechanism. METHODS: The cellular protection of chlorophyllin against oxidative damage was detected by cell-survival assay with flow cytometry. The level of free radicals was detected directly by electron spin resonance spectra. The induced expression of HO-1 was shown by RT-PCR, Western blot, immunofluorescence confocal laser microscopy and enzymatic activity test. Whether the activation of PI3K/Akt pathway was involved was detected by Western blot. RESULTS: Chlorophyllin could protect HUVEC against oxidative damage caused by H2O2 via scavenging the excessive free radicals. Chlorophyllin treatment could induce expression of HO-1 in a dose- and time-dependent manner. The activation of PI3K/Akt pathway was required in the induction of HO-1. LY294002, the specific inhibitor of PI3K, could suppress the activation of PI3K/Akt and the induced expression of HO-1 in a dose-dependent manner. CONCLUSIONS: Chlorophyllin shows cellular protection against oxidative damage by counteracting the excessive free radicals. Up-regulation of HO-1 expression plays a pivotal role in the protection of chlorophyllin, while the activation of PI3K/Akt signaling pathway is required in the induction of HO-1.

Early embryonic sensitivity to cyclophosphamide in cardiac differentiation from human embryonic stem cells.

hESCs (human embryonic stem cells) can differentiate into tissue derivatives of all three germ layers in vitro and mimic the development of the embryo in vivo. In this study, we have investigated the potential of an hESC-based assay for the detection of toxicity to cardiac differentiation in embryonic development. First of all, we developed the protocol of cardiac induction from hESCs according to our previous work and distinguished cardiac precursor cells and late mature cardiomyocytes from differentiated cells, demonstrated by the Q-PCR (quantitative real-time PCR), immunocytochemistry and flow cytometry analysis. In order to test whether CPA (cyclophosphamide) induces developmental and cellular toxicity in the human embryo, we exposed the differentiating cells from hESCs to CPA (a well-known proteratogen) at different stages. We have found that a high concentration of CPA could inhibit cardiac differentiation of hESCs. Two separate exposure intervals were used to determine the effects of CPA on cardiac precursor cells and late mature cardiomyocytes respectively. The cardiac precursor cells were sensitive to CPA in non-cytotoxic concentrations for the expression of the cardiac-specific mRNA markers Nkx2.5 (NK2 transcription factor related, locus 5), GATA-4 (GATA binding protein 4 transcription factor) and TNNT2 (troponin T type 2). Non-cytotoxic CPA concentrations did not affect the mRNA markers' expression in late mature cardiomyocytes, indicating that cardiac precursors were more sensitive to CPA than late cardiomyocytes in cardiogenesis. We set up the in vitro developmental toxicity test model so as to reduce the number of test animals and expenses without compromising the safety of consumers and patients. Furthermore, such in vitro methods may be possibly suited to test a large number of chemicals than the classical employed in vivo tests.

Dynamic changes of heme oxygenase-1 in the hippocampus of rats after acute carbon monoxide poisoning.

Heme oxygenase-1 (HO-1), an inducible enzyme, degrades heme to carbon monoxide (CO), iron, and bilirubin. We have investigated the relationship among HO-1 protein expression, HO activity, and CO concentrations in the hippocampus of CO-exposed rats. Western blotting and immunohistochemistry revealed that the enzyme is predominantly localized in hippocampal CA1 and CA3 pyramidal cells and in granule cells of the dentate gyrus. HO enzyme activity was reduced immediately following CO exposure, while expression of HO-1 protein was consistently upregulated in a time-dependent manner. Local CO concentrations in hippocampus rose immediately following exposure, but the elevation was maintained for ~20 h despite the decline in blood carboxyhemoglobin levels toward baseline. We suggest that CO initially inhibits HO enzyme activity, whereas at later time points the inhibition is released and local CO generation is maintained by the activity of the endogenous HO enzyme. And the noninducible form of heme oxygenase, HO-2, was not altered following CO administration. Together these results indicate that the HO/CO pathway in the rat hippocampus is induced by acute CO exposure; local CO production may play a regulatory role in brain injury following CO poisoning.

[Effects of baicalin on pulmonary functions of acute respiratory distress syndrome induced by oleic acid in rats].

OBJECTIVE: To investigate the effect of baicalin on pulmonary functions and its mechanism during the development of acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats. METHODS: Rats were randomized into 5 groups: control, ARDS (OA induction, 0.12 mg/kg), baicalin-treated group (150 mg/kg), baicalin-treated group (300 mg/kg) and baicalin-treated group (450 mg/kg). The blood samples and lung tissue were collected at 10 min, 1, 2 and 6 h after OA injection. The lung concentration of myeloperoxidase (MPO) was detected by an ELISA (enzyme-linked immunosorbent assay) kit. Meanwhile, blood gas analysis and pulmonary pathological examination were also performed. RESULTS: The level of arterial oxygen partial pressure and oxygenation index decreased (P < 0.01 vs. control) and oxygenation index (190 mm Hg, 1 mm Hg = 0.133 kPa) reached the diagnostic standard of ARDS at 2 h in ARDS group. In baicalin-treated group (150 mg/kg and 300 mg/kg), the level of arterial oxygen partial pressure and oxygenation index increased versus the ARDS group. In baicalin-treated group (450 mg/kg), the level of arterial oxygen partial pressure was undifferentiated at 1, 2 and 6 h (P > 0.05) and decreased at 10 min (46.8 mm Hg, P < 0.05) versus the ARDS group. The level of MPO increased in baicalin-treated (300 mg/kg) and ARDS groups. Compared with the ARDS group, the level of MPO decreased significantly in baicalin-treated group (300 mg/kg) at 10 min, 1 and 2 h. Meanwhile, the pulmonary pathological damage improved in baicalin-treated group (300 mg/kg). CONCLUSION: An appropriate dose of baicalin may improve hypoxemia of ARDS induced by OA in rats. It may be due to the inhibition of MPO activity.

Immunosuppressive activity of a cycloartane triterpene glycoside from Beesia calthaefolia by inhibiting T cell proliferation.

BC-1 is a cycloartane triterpene glycoside isolated from the whole plant of Beesia calthaefolia. Our recent studies proved that BC-1 inhibited proliferation of splenic lymphocyte and phagocytosis of macrophages, and inhibited the increased production of TNF-α and IL-1ß. However, it lacks of study about the immunomodulatory effect of BC-1 on purified T lymphocytes. Therefore, in the present study, we evaluated the suppressive potentials of BC-1 on immune responses in vitro. BC-1 markedly suppressed anti-CD3/CD28 mAbs (mAbs) induced murine T lymphocytes proliferation, the expression levels of CD69 and CD25 of CD3+ T cells. BC-1 could strongly decrease ratio of CD4+/CD8+, decrease the Th1/Th2 cytokines production (IL-2, IFN-γ, IL-4, and IL-10) of CD4+ T-cells. In addition, we studied signal transduction pathways about T-cell activation on puried murine CD4+ T lymphocytes by western-blot assay. The data revealed that BC-1 could inhibit the activation of JNK, ERK and PI3K/AKT signal transduction pathways. These results indicated that BC-1 possesses potential downregulating effect on the immune system and might be developed as an immunosuppressive agent in treatment of CD4+ T cell-mediated inflammatory and undesired immune responses.

[Dynamic changes of hemorheology in rats after carbon monoxide poisoning].

OBJECTIVE: To investigate the startup detail of circulation dysfunction and its role in the progress of delayed neuropsychologic sequelae (DNS) after carbon monoxide (CO) poisoning with comparison with the model of ischemia-reperfusion. METHODS: The ischemia-reperfusion rat model was established by Pulsinelli-Brierley method, and the CO poisoning rats model by i.p. injected with CO repeatedly respectively, and the rats were identified with DNS following the experiment of pathology and the ethnology. RESULTS: The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen increased significantly immediately after reperfusion, and recovered gradually with the ischemia-reperfusion rat model. The whole blood viscosity decreased significantly immediately after CO treated i.p. Especially at low shear rate, the hematocrit also declined remarkably in the early stage after CO treatment. But 1day later, these parameters turned to the trend of the ischemia-reperfusion rats. There was a prominent elevation of both indexes until the 14th day following CO injection i.p. CONCLUSION: There are significantly sustained hyper-coagulation and hyper-viscosity with circulation in rats after CO poisoning compared with ischemia-reperfusion model during the period of DNS, which might contribute to increase cerebral circulation resistance, blocked blood flow, and deteriorate hypoxemia in progression of DNS.

[Effects of exogenous carbon monoxide on neurocytes: experiment in vitro].

OBJECTIVE: To study the effect of CO on neurocytes. METHODS: Human neuroblastoma cells of the line SH-SY5Y were cultured and exposed to CO of the concentrations of 100, 1000, and 10 000 ppm for 12 h, and some SH-SY5Y cells were cultured and exposed to 5% CO(2) to be used as control group. The cell viability was observed with MTT assay. The DNA content and percentage of apoptosis were measured by flow cytometry and DNA agarose gel electrophoresis. Laser scanning confocal microscopy (LSCM) was used to detect the reactive oxygen species and the reduction in mitochondrial membrane potential. The activation of caspase-3 was measured with the caspase-3 activity assay kit. The expression of Bax was detected with Western blotting. RESULTS: After exposure to 1000 and 10 000 ppm CO for 12 h the viability of the cells decreased to 85.6 +/- 9.2 and 63.4 +/- 8.1 respectively (both P < 0.05), the apoptotic rates of the cells were 29.03% and 41.67% respectively, DNA agarose gel electrophoresis showed clear DNA ladder band, the caspase-3 activity increased by 129% and 443% respectively, LSCM showed that the number of the SH-SY5Y cells decreased and the fluorescence intensity inside the cells increased significantly (both P < 0.05), the red/green fluorescence ratio inside the cells decreased from the baseline level of (5.91 +/- 0.21) to (1.56 +/- 0.07) and (0.34 +/- 0.02) respectively, and the Bax protein expression increased greatly. However, 100 ppm CO had no obvious effects on the cell viability, reactive oxygen species, mitochondrial membrane potential, caspase-3 activity, and expression of Bax. CONCLUSION: High concentration CO has direct cytotoxicity on neurocytes cultured in vitro, but low concentration CO does not induce marked injuries of neurocytes.

Dynamic changes of heme oxygenase-1 and carbon monoxide production in acute liver injury induced by carbon tetrachloride in rats.

Heme oxygenase-1, a stress-responsive enzyme that catabolizes hemes into carbon monoxide, biliverdin, and iron, has been shown to play a pivotal role in many physiological and pathological situations. Here we investigated changes in HO-1 enzyme activity and protein expression, and its end product carbon monoxide concentrations in the liver of rats after CCl(4) treatment. We found that CCl(4) administration not only induced severe liver damage in rats, as demonstrated by dramatic elevation of ALT, AST levels and severe histopathological changes, but also resulted in a prominent up-regulation of HO-1 enzyme activity. Western blot and immunohistochemical analysis confirmed that expression of HO-1 protein was also increased significantly in a time-dependent manner following CCl(4) treatment, and localized mainly in liver cells around the central vein. In addition, CO concentrations in the liver of CCl(4)-treated rats were elevated remarkably in the same time-dependent way as HO-1 induction in contrast to the control rats. These data indicated that HO-1/CO pathway was greatly up regulated in the liver of rats after CCl(4) treatment, which might play an important protective role in the pathophysiological mechanism underlying CCl(4)-induced hepatotoxicity. It therefore suggested that more relevant studies should be carried out in the future to clarify the detailed mechanisms.

Effects of salvianolic acids on erythrocyte deformability in oleic acid induced acute lung injury in rabbits.

The present study was to investigate the protective effects of salvianolic acids (SA) on deformability of red blood cells (RBCs) and its mechanism during the development of acute lung injury (ALI) induced by oleic acid (OA) in rabbits. 32 rabbits were randomized into four groups, normal control group, OA-treated group (0.15 ml/kg), SA-treated group and OA+SA treated group. The blood samples were collected at 0, 10, 30, 60, 90, 120 and 180 min after OA injection. The RBC deformation index, Orientation index and small deformation index were measured by ektacytometry. The concentration of malondialdehyde (MDA) in RBCs was detected by the assay kit. Meanwhile, the pulmonary pathological examination and the blood gas analysis were also performed. The results showed that the deformation index, orientation index and small deformation index decreased during the early phase of ALI, while the concentration of MDA in RBCs increased during the course. Pre-treatment with SA increased the deformability and orientability of RBC significantly and decreased the concentration of MDA in RBCs compared with OA group. Meanwhile, the hypoxia and pulmonary pathological damage were much improved. These results suggest that there were erythrocyte deformability changes in the early phase of ALI. SA has the protective effects on erythrocyte deformability during the development of ALI induced by OA, which might be due to its antioxidant effect. These results are valid in rabbits and in a model of ARDS, it would be interesting to see the effects of SA in patients.

[Protective effect of heme oxygenase-1 and its reaction product, carbon monoxide on acute liver injury induced by carbon tetrachloride in rats].

OBJECTIVE: To investigate the protective role of heme oxygenase-1 and its reaction product, carbon monoxide against acute liver injury induced by carbon tetrachloride in rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into six groups with five in each. The control group received a single dose of corn oil injection. Carbon tetrachloride was injected intraperitoneally (i.p) to establish acute liver injury models in rats. Hemin(50 micromol/kg) was administered i.p. 12 hours before CCl(4) treatment, with an aim to induce HO-1 protein expression in the liver of rats. Carbon monoxide was injected i.p. 12 hours prior to CCl(4) injection, resulting in about 8%-12% carboxyhemoglobin concentration in vivo. The expression of HO-1 in the liver of hemin-treated rats was determined by western blot method at different time points. At 24 h after carbon tetrachloride administration, all rats were sacrificed to collect blood samples for the examination of ALT, AST levels and to remove liver tissues for analysis of MDA concentration, SOD activity and caspase-3 activity as well as TNF-alpha contents. In addition, histopathological changes were investigated and hepatocyte apoptosis was detected by TUNEL method. RESULTS: The administration of carbon tetrachloride to rats caused a marked hepatic damage, characterized by significant elevation of serum ALT, AST levels(2 136.3+/-163.4 U, 1 422.7+/-221.7 U) and liver MDA content(5.28+/-0.93 micromol/g), caspase-3 activity (optical density value 4.69+/-1.02) and TNF-alpha level(256.3+/-27.3 ng/L) combined with a remarkable reduction in liver SOD activity (45.9+/-14.8 U/mg) as compared with the control rats. Histopathological observations revealed severe damage in the liver and prominent hepatocyte apoptosis took place in CCl(4) -treated rats. However, pretreatment with hemin could induce high expression of HO-1 protein and exert potent protective effects against liver injury, as demonstrated by a significant decrease in ALT, AST levels(287.1+/-24.3 U, 246.2+/- 21.7 U) and MDA concentration(3.27+/-1.34 micromol/g), reduction in caspase-3 activity(optical density value 2.49+/-1.47) and TNF-alpha level(132.6+/-19.5 ng/L), as compared with the CCl(4) -treated rats. Moreover, hepatocyte apoptosis and liver injury were both attenuated remarkably in the liver of rats pretreated with hemin. In contrast to hemin administration, single injection of exogenous CO produced the same protective effects, as indicated by the remarkable reduction of ALT, AST levels and caspase-3 activity and TNF-alpha levels. CONCLUSION: The above results suggest that HO-1/CO system has a potent protective effect on acute liver injury induced by carbon tetrachloride in rats. Induction of HO-1 expression and low concentration of CO can inhibit the progress of hepatic damage, which might be due to the alleviation of lipid peroxidation and reduction of caspase-3 activity or inhibition of TNF-alpha level.

[Expression of Fas antigen and Fas ligand in acute liver injury induced by carbon tetrachloride in rat].

OBJECTIVE: To investigate the dynamics of expression of Fas antigen and Fas ligand (FasL) in a rat model of carbon tetrachloride-induced acute liver injury, and explore the role of apoptosis in liver injury. METHODS: Thirty-five healthy male Wistar rats were randomly divided into normal control group and experiment group, and the latter group was divided into six subgroups: 3, 9, 16, 24, 36 and 48 hours groups with 5 rats in each group. The liver injury was induced by carbon tetrachloride. Sections of liver tissue were stained with hematoxylin and eosin and observed under optical microscope. Fas antigen and FasL in rat liver were determined at different time points with immunohistochemical method. Hepatocytes apoptosis were observed with terminal deoxynucleotidyl-transferase mediated dUTP-biotin nick end labeling (TUNEL) method. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in the liver tissues were analyzed at the same time point. Serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels were also determined. RESULTS: Fas antigen and FasL were expressed in the liver tissues of control rats. Following carbon tetrachloride challenge, severe liver injury took place in rats as revealed under microscope and a large amount of hepatocytes apoptosis was found. Hepatic Fas and FasL expression were both increased markedly from 3 to 48 hours after carbon tetrachloride challenge in experiment group. Liver MDA concentration and serum ALT and AST were elevated significantly, while SOD activity decreased remarkably in the experiment group compared with control group (P<0.05 or P<0.01). CONCLUSION: Expression of Fas/FasL is remarkably induced in acute liver injury and accords with the changes of hepatocytes apoptosis, which suggests that apoptosis mediated by Fas/FasL may play an important role in the pathogenesis of acute liver injury.

One new cycloartane triterpene glycoside from Beesia calthaefolia.

One new cycloartane triterpene glycoside (1) was isolated from the whole plant of Beesia calthaefolia. Its structure was elucidated on the basis of extensive spectroscopic data analysis. Its inhibitory effect was measured by the classical pathway of the complement system, and compared with those of known related cycloartane glycosides 2 and 3, previously isolated by us from the same plant. Compounds 1 and 2 exhibited inhibitory activity of complement system with IC50 of 395.3 and 214 µM, respectively. The results suggested that OH at C-12, C-18 and C-15 along with the polarity could affect the inhibitory activity.

[Preventive effects and mechanism of heme oxygenase-1 activation on acute respiratory distress syndrome in rats].

OBJECTIVE: To explore the possible mechanism of heme oxygenase-1 (HO-1) induction for its protective effects on acute respiratory distress syndrome (ARDS). METHODS: The production of HO-1 was induced by hemoglobin (Hb) injection into oleic acid (OA) induced ARDS rats. Western blot and RT-PCR techniques were used to observe the induction of HO-1 in vivo. Both the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). Combined with blood gas analysis and other indexes, the effect of HO-1 on ARDS could be clearly manifested. RESULTS: The expression of HO-1 mRNA was increased significantly 16 h after Hb injection, and the protein expression of HO-1 was also obviously increased 24 h later (P < 0.01). The levels of TNF-alpha and IL-8 in both serum and BALF were significantly lower in Hb + OA group than in OA group (P < 0.01). Arterial blood PaO(2), oxygen saturation, and oxygenated index in Hb + OA group [(56.28 +/- 6.71) mm Hg, (79.53 +/- 5.82)%, and (258.81 +/- 29.37) mm Hg respectively] were higher than in OA group [(35.08 +/- 4.59) mm Hg, (55.80 +/- 12.76)%, and (167.86 +/- 21.94) mm Hg]. Lung wet and dry weight, and pathological changes were also improved. CONCLUSION: The production of HO-1 was successfully induced by hemoglobin in vivo. Protective effects of HO-1 on ARDS might be related to the decreasing in inflammatory factors, such as TNF-alpha and IL-8.

Salvianolic acids attenuate rat hippocampal injury after acute CO poisoning by improving blood flow properties.

Carbon monoxide (CO) poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP) occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA) on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct), plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA) levels in red blood cells (RBCs). These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning.