The central role of corticotropin-releasing hormone in stress-induced hyperthermia and LPS-induced fever in rats

AIM:To further investigate the role of central corticotropin-releasing hormone in stress-induced hyperthermia and lipopolysaccharide (LPS)-induced fever in the rat.METHODS:Test substances were administered intracerebroventricularly (icv) via a third ventricle cannula. Body temperature responses were monitored at 30 min intervals using colonic thermistor probes. Arginine vasopressin (AVP) level in the ventral septal area (VSA) determined by radioimmunoassay. RESULTS:In normal saline controls,rats were handled to take the colonic temperature,their body temperature significantly increased with a peak of(0.88±0.31)℃.The injection(icv)of α-helical CRH(9-41),a CRH-41 receptor antagonists,markedly attenuated the stress-induced hyperthermia within 90 min after injection of normal saline.LPS(300 ng,icv)stimulated a biphasic rise in the colonic temperature,the 3.5 h thermal response index(TRI_3.5)and AVP levels in the VSA of LPS-treated rats were higher than those of control rats.The AVP responses to LPS were inhibited significantly by blockade of central CRH actions using α-helical CRH(9-41)(5μg,icv)administered 10 min prior to LPS,whileα-helical CRH(9-41)(5μg,icv)resulted in exacerbated febrile responses to LPS(300 ng,icv). CONCLUSION:Central CRH plays an important role in stress-induced hyperthermia. The injection (icv) of α-helical CRH(9-41) enhances markedly LPS-induced fever in rats. CRH is a dual action molecule in LPS-induced fever, which itself mediates LPS-induced fever, at the same time, and limits the rise in body temperature during fever through actions of AVP in the VSA and glucocoticoids.     

Effect of Qing-Kai-Ling Injecta on cAMP content of hypothalamus and AVP content in ventral septal area of endotoxin-induced febrile rabbits

AIM:To investigate the mechanism of Qing-Kai-Ling(QKL) Injecta suppressing endotoxin(ET)-induced fever in rabbits.METHODS:①The ET-induced fever model was established in rabbits. QKL injecta was administered intravenously, and the febrile response of rabbits was observed. The cAMP content in the hypothalamus (HP) and arginine vasopressin (AVP) content in the ventral septal area (VSA) were determined by radioimmunoassay.RESULTS:①The maximal increment in body temperature (△T) ,6 h thermal response index (TRI₆)(29.59±10.39), cAMP content in the HP and AVP content in the VSA in the ET group were significantly higher than those in the normal saline (NS) group and the QKL+ET group .②The positive correlation was observed between the cAMP content in the HP and the fluctuation of body temperature (r=0.904,P＜0.01).CONCLUSION:The antipyretic mechanisms of QKL were probably due to inhibiting the increase in cAMP content in HP, and meanwhile stimulating the release of AVP in VSA.     

Effects of phosphodiesterase inhibitor-induced insulin resistance on glucose and lipid metabolism in rats

AIM:To investigate the effects of milrinone (a selective phosphdiesterase III inhibitor PDE₃) on insulin secretion, blood glucose, plasma free fatty acids (FFA) and dose-response relationship, and assess possible effects of milrinone on glucose metabolism and insulin sensitivity in conscious rats.METHODS:The catheterized nonstressed rats were administered by the varying doses of milrinone (1, 5, 25 μmol/kg) and were compared with controls. A hyperinsulinaemic- euglycaemic clamp was established in awake rats, and milrinone(25 μmol/kg) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 min during hyperinsulinaemic- euglycaemic clamp. Glucose turnover was decided by gas chromatograph mass spectrometer (GC-MS).RESULTS:After dosing, plasma FFA levels in 3 milrinone groups significantly increased compared with the controls and before dosing. The percentages of elevation of FFA by the different milrinone doses were very similar, 50%, 52%, 55% for 1, 5, 25 μmol/kg respectively at 2 min after dosing. Plasma insulin levels were significantly elevated in the 5 and 25 μmol/kg groups, and the effect of milrinone on glucose concentration was detectable only 25 μmol/kg group. During hyperinsulinaemic clamp, there were significant increase in plasma FFA (from 173.1±15.2 to 633.8±87.3 μEq/L) and hepatic glucose production (HGP), and a significant decrease in glucose infusion rates (GIR) (to about 21%).CONCLUSION:These data suggest that milrinone impaires the abilities of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization in peripheral tissue. Therefore, milrinone administration may induce an acute insulin resistancein vivo.     

Effects of aminoguanidine on endotoxin-induced acute lung injury in rabbits

AIM: To observe the effect of aminoguanidine (AG) on hemodynamics and lung capillary permeability in acute lung injury (ALI) in rabbits. METHODS:24 rabbits were equally divided into four groups: saline group, endotoxin group, AG group and AG plus endotoxin group. In AG plus endotoxin group, endotoxin was injected to animals to make an ALI model, 25mg/kg AG was injected following that and let this sustain 3 hours. Meanwhile, mean arterial pressure (MAP), mean pulmonary arterial pressures (MPAP) and blood gas analyses were observed during this period. At the end of the experiment, broncho-alveolus lavage was performed, pathologic samples were treated routinely and lung wet weight/dry weight ratio was calculated. RESULTS:After endotoxin injection, MAP and arterial oxygen pressure (PaO₂) decreased, and MPAP increased significantly. The injection of AG had little effect on MAP, but AG could markedly decrease MPAP and increase PaO₂. Cell count in broncho-alveolus lavage fluid (BALF) was less in AG plus endotoxin group than in endotoxin group. Although AG did not affect total protein in BALF, low molecular weight proteins decreased in AG plus endotoxin group by the assay of electrophoresis. Tissue wet weight/dry weight ratio also decreased in this group. Pathologic study showed that there were fewer inflammatory cells and less lung edema in AG plus endotoxin group. CONCLUSION:AG could improve hemodynamics status and attenuate acute lung injury induced by endotoxin in rabbits.     

Synergetic antagonism of polymyxin B associated with glycine to pyrogenous effect of endotoxin

AIM and METHODS: To investigate the antagonistic effects of polymyxin B(PMB) in combination with glycine(Gly) on the pyrogenicity of endotoxin(ET) in rabbits and the LD₅₀ of PMB in mice. RESULTS: (1)The antagonistic effect of PMB plus Gly was augmented and the optimal combination was PMB(30000 U) plus Gly(15 mg) to ET(0.01 μg); (2)The LD₅₀ of PMB with or without Gly were 8.38×10⁴U/kg and 6.06×10⁴ U/kg in mice, respectively. CONCLUSION: The antagonistic effect of PMB plus Gly on ET showed synergnism and this combination could decrease the toxicity of PMB.     

Effects of perindopril at different doses on cardiac function and ACE2/Ang-(1-9)/Ang-(1-7) axis of ischemic cardiac dysfunction rabbits

AIM: To investigate the different dose of perindopril on cardiac function in the rabbits with ischemic cardiac dysfunction. METHODS: Male rabbits weighing 2.5~3.0 kg(n=30) were randomly divided into 3 groups(n=10):high dose perindopril group(HD group), low dose perindopril group(LD group) and cardiac dysfunction group(CD group). The Left anterior descending coronary artery of the rabbits was ligatured for model preparation. In HD group, the rabbits were treated with perindopril split normal saline solution(1 g/L)2 mL·kg^-1·d^-1. In LD group, the rabbits were treated with perindopril split normal saline solution(0.33 g/L)2 mL·kg^-1·d^-1. In CD group, the rabbits were treated with normal saline solution 2 mL·kg^-1·d^-1. Four weeks after treatment, the cardiac function was measured via echocardiography, the mRNA expression of angiotensin-converting enzyme 2(ACE2) and angiotensin type 2 receptor(AT2R) was analyzed by real-time PCR, serum angiotensin(Ang)-(1-9) and Ang-(1-7) levels were detected by ELISA. RESULTS: Compared with CD group, the cardiac function of the 2 groups treated with perindopril was significantly improved(P<0.01), and more improvement in HD group was observed than LD group(P<0.05). The serum angiotensin(Ang)-(1-9) and Ang-(1-7) level and the mRNA expression of ACE2 and AT2R in the 2 groups treated with perindopril were significantly improved(P<0.01). Compared with LD group, the mRNA expression of ACE2 and AT2R and the serum levels of Ang-(1-9) in HD group were significant improved(P<0.05), while no difference of serum Ang-(1-7) level was observed. Correlation analysis revealed that the improvement of the cardiac function was associated with serum Ang-(1-9) level, mRNA expression of ACE2 and AT2R(P<0.01), but has no significant correlation with serum Ang-(1-7) level. CONCLUSION: High dose of perindopril may improve more cardiac function in ischemic cardiac dysfunction model in rabbits. The mechanism may relate to increasing serum Ang-(1-7) level to activate AT2R.     

Role of PI3K/Nrf2 signaling pathway in endotoxin-induced acute kidney injury in rabbits

AIM: To evaluate the role of phosphatidylinositol 3-kinase/nuclear factor E2-related factor 2 (PI3K/Nrf2) signaling pathway in endotoxin-induced acute kidney injury in rabbits. METHODS: Healthy male New Zealand white rabbits were randomly divided into 5 groups: control group (group C), LPS group (group L), wortmannin+LPS group (group WL), wortmannin group (group W) and dimthyl sulfoxide (DMSO) group (group D). Wortmannin at dose of 0.6 mg/kg was injected via the auricular vein in groups W and WL, DMSO at concentration of 0.08 mL/kg was injected in group D, while normal saline (0.08 mL/kg) was injected in groups C and L. LPS at dose of 5 mg/kg was injected via the auricular vein in groups L and WL 30 min later, and equal volume of normal saline was injected in group C, D and W for control. The rabbits were sacrificed 6 h after LPS or normal saline administration. The kidneys were removed for microscopic examination and the determination of histological scores of kidney (HSK). The concentrations of blood urea nitrogen (BUN) and creatinine (Cr), urinary α1-microglobulin (α1-MG), MDA content, SOD activity, the mRNA expression of Nrf2 and HO-1, and the protein levels of total Akt, p-Akt, total Nrf2, p-Nrf2, nuclear Nrf2 and HO-1 in the renal tissues were also detected. RESULTS: Compared with groups C, D and W, the concentrations of BUN and Cr, urinary α1-MG concentration, MDA content and HSK were significantly increased, while SOD activity was significantly decreased (P<0.05). The mRNA expression of Nrf2 and HO-1, and the protein levels of p-Akt, total Nrf2, p-Nrf2, nuclear Nrf2 and HO-1 in the renal tissues were significantly increased in groups L and WL. No significant change among groups C, D and W was observed. Compared with group L, the concentrations of BUN and Cr, urinary α1-MG concentration, MDA content and HSK were significantly increased, while SOD activity, the mRNA expression of Nrf2 and HO-1, and the protein levels of p-Akt, total Nrf2, p-Nrf2, nuclear Nrf2 and HO-1 in the renal tissues were significantly decreased in group WL. CONCLUSION: Activation of PI3K/Nrf2 signaling pathway may be one of the regulatory mechanisms of the body adapting to the endotoxin-induced acute kidney injury in rabbits.     

Effect of Nao-re-qing oral liquid on cAMP content in hypothalamus and CSF,and AVP content in ventral septal area of endotoxin-induced febrile rabbits

AIM: To explore the mechanism of Nao-re-qing oral liquid (NRQ) decreasing endotoxin (ET)-induced fever in rabbits. METHODS: (1) The ET-induced fever model was established in rabbits. Febrile response of rabbits was observed. (2) The arginine vasopressin (AVP) content in the ventral septal area (VSA), and cAMP content in hypothalarmus (HP) and CSF were determined by radioimmunoassay.RESULTS: (1) In ET group, the maximal increment in body temperature (ΔT) [(1.80±0.16) ℃], 6 h thermal respone index (TRI₆)(11.31±0.20), the cAMP content in the HP [(1.35±0.21)nmol/g], the cAMP content in CSF [(66.69±1.82) nmol/L] and AVP content in the VSA [(30.80±9.59)ng/g ] were significantly higher than those in NRQ+ET group[ΔT(0.82±0.08) ℃, TRI₆(5.73±0.09), HP: cAMP(0.70±0.50)nmol/g, CSF: cAMP(56.86±1.34), AVP:(11.91±3.47)ng/g]( P<0.01). (2) The AVP content in VSA, and cAMP content in HP and CSF were separately paralleled with the fluctuation of body temperature (AVP: r=0.972, P<0.01; HP: cAMP r=0.899, P<0.05; CSF: cAMP r=0.991, P<0.01). CONCLUSION: The antipyretic action of NRQ may be due to inhibiting the increase in cAMP in HP and meanwhile promoting the release of AVP in VSA.     

Effects of granulocyte colony-stimulating factor on the myocardial infarction in experimental rats

AIM: To investigate the effects of granulocyte colony-stimulating factor (G-CSF) on the myocardial infarction in experimental rats. METHODS: Rats were randomly divided into GT group and saline control group (SC).The rats of GT group were treated with G-CSF (10 μg/kg) once a day subcutaneously for 5 days and those of SC group were received saline.On the third day, both groups were injected with isoprenaline (ISO) interaperitoneally to develop acute ischemic model. The hearts were harvested from 2 weeks to 4 weeks after administration of ISO for histopathological examination. RESULTS: Compared with saline control group, G-CSF treatment group significantly reduced the scar size (P<0.05). We also found the regeneration of myocytes, smooth muscle and endothelial cells. CONCLUSION: G-CSF treatment could be benefical to the regeneration of infarcted myocardium and significantly reduce scar size and it could be used for therapeutic intervention of the acute myocardial infarction.     

Role of PAR-2 in tryptase mediated IEC-6 cell injury

AIM: To investigate the role of protease activated receptor-2 (PAR-2) in the process of tryptase mediated IEC-6 cell injury. METHODS: The rat intestinal epithelial cell line IEC-6 was treated with tryptase at different concentrations (1 μg/L, 10 μg/L, 100 μg/L and 1 000 μg/L) in the presence or absence of PAR-2 antagonist FSLLRY-NH2 for 12 h respectively. The cell survival rate was detected by MTT assay. The protein levels of PAR-2 and cleaved-caspase 3 were determined by Western blotting. The LDH activity was also measured. RESULTS: Compared with control group, the cell survival rates were significantly decreased in 100 μg/L and 1 000 μg/L tryptase treated groups, the LDH activities were significantly increased in 10 μg/L to 1 000 μg/L tryptase treated groups, and the protein levels of PAR-2 and cleaved caspase 3 were significantly increased in 100 μg/L and 1 000 μg/L tryptase treated groups (P<0.05). Compared with 1 000 μg/L tryptase treated group, the LDH activity and cleaved caspase 3 protein level were dramatically decreased while the survival rate was significantly increased in the presence of PAR-2 antagonist FSLLRY-NH2 (P<0.05). CONCLUSION: Tryptase induces IEC-6 cell injury in a dose-dependent manner by activating PAR-2.     

Effect of glycine on lipopolysaccharide and hypoxia-induced necrotizing enterocolitis in rats

AIM:To investigate the effect of glycine on endotoxin and hypoxia-induced necrotizing exterocolitos (NEC) in rats. METHODS:In glycine+NEC group, twenty anesthetized and artificially ventilated rats received 1g/kg glycine (20%, iv). Five minutes later, the rats were treated with 2 mg/kg lipopolysaccharide (LPS). In control group (NS+NEC), twenty rats were treated with normal saline as a substitute for glycine. In all animals, FiO₂ was reduced after 90 min from 21% to 5% and ventilation continued until 180 min or death. At the end of the experiment, the samples of blood and intestine were obtained immediately. Serum TNFα was measured with ELISA, serum NO was determined by nitrate reductase. The histopathology of the necrotic lesions were categoried: grade Ⅰ, focal mild injury confined to villous tips; grade Ⅱ, partial loss of villi; grade Ⅲ, necrosis extending to submucosa; grade Ⅳ, transmural necrosis. RESULTS:The survival time was shorter in the NS+NEC group (P＜0.01). The intestinal injury of the rats in glycine+NEC group was markedly alleviated (P＜0.01). The levels of TNF-α and NO₂^-/NO₃^- in serum decreased significantly in animals treated with glycine (P＜0.01, P＜0.05). CONCLUSION:Glycine alleviated LPS-induced NEC by inhibiting excessive production of TNFα and nitric oxide.     

Dexmedetomidine attenuates acute alcoholic hepatic injury in mice

AIM: To investigate the effects of dexmedetomidine (DEX) on acute alcoholic hepatic injury in mice and to explore the possible mechanisms. METHODS: Kunming mice (n=50) were randomly divided into 5 groups (n=10): normal saline control (NS) group, acute alcoholic hepatic injury model (E) group, low-dose (10 μg/kg) DEX (E+L) group, medium-dose (50 μg/kg) DEX (E+M) group and high-dose (100 μg/kg) DEX (E+H) group. The animals were sacrificed at 6 h after gavage of alcohol or normal saline. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) were measured. The livers were removed for evaluation of histological characteristics and determining the content of tumor necrosis factor-α (TNF-α) amd interleukin-1β (IL-1β) in the liver tissues by ELISA. The expression levels of cytochrome P450 2E1 (CYP2E1) and nuclear factor-κB (NF-κB) in the liver tissues were evaluated by Western blot. RESULTS: Compared with NS group, the levels of ALT, AST and TG were obviously increased in E group, which were obviously decreased in E+M and E+H groups. Compared with NS group, the levels of TNF-α, IL-1β and MDA were obviously increase in E group, which were obviously decreased in E+M and E+H groups. Compared with NS group, the activity of SOD and the content of GSH were obviously decreased in E group, which were obviously increased in E+M and E+H groups. Compared with NS group, the expression of CYP2E1 and NF-κB was obviously increase in E group, which was obviously decreased in E+M and E+H groups. Compared with NS group, ethanol induced marked liver histological injury, which was less pronounced in E+M and E+H groups. CONCLUSION: DEX has a protective effect on mouse liver with acute alcoholic injury by the involvement in the processes of antioxidation and antiinflammation, and its mechanism may be associated with the inhibition of CYP2E1 and NF-κB expression.     

Role of morphine and gp120 V3 loop in learning and memory dysfunction in rats

AIM: To explore the role of morphine and gp120 V3 loop in learning and memory dysfunction in rats. METHODS: SD rats (4~6 weeks old) were infused by the intracerebroventricular injection with gp120 V3 loop and morphine. The Morris water maze was used to evaluate spatial memory. The apoptotic cells in the hippocampal zone were observed by TUNEL staining. The protein level of p-ERK was determined by Western blot. RESULTS: Compared with control group, the rats exhibited a longer latency to escape the hidden platform, shorter retention and less frequency of crossing target quadrant in 100 μg/kg morphine group, 200 μg/kg morphine group and gp120 V3 loop group. The TUNEL positive cells in the hippocampal zone of the rats in 100 μg/kg morphine group, 200 μg/kg morphine group and gp120 V3 loop group were increased. The levels of p-ERK were also increased in 100 μg/kg morphine group, 200 μg/kg morphine group and gp120V3 loop group as compared with the controls. The same results were observed in 200 μg/kg morphine + gp120 V3 loop group as compared with 200 μg/kg morphine group or gp120 V3 loop group. CONCLUSION: Intracerebroventricular injection of gp120 V3 loop induces learning and memory dysfunction in SD rats, and morphine enhances this effect. The mechanism may be related to the combined effect on the increase in p-ERK by gp120 V3 loop and morphine.     

Effects of aflatoxin G1 on proliferation and TNF-αsecretion of human peripheral blood mononuclear cells in vitro

AIM: To explore the effects of aflatoxin G₁(AFG₁ )on proliferation and TNF-α secretion of human peripheral blood mononuclear cells(HPBM) in vitro. METHODS: The effects of AFG₁ on proliferation of HPBM were analysed with flow cytometric (FCM) DNA analysis and MTT bioassay, while that on TNF-α secretion was detected with ELISA.RESULTS: FCM analysis revealed that 6 h after treatment, proliferation index(PI) of 1000 μg/L AFG₁ treated HPBM was significantly higher than that of control. 24 h after AFG₁ treatment, stimulating effects on proliferation was found in HPBM treated with AFG₁ at 200 μg/L and 1 000μg/L.Regression analysis showed that PI was postively correlated with the concentrations of AFG₁ in the concentration range from 0 to 1 000μg/L( r=0. 5122 and 0.5119 respectively,P＜0.05).MTT bioassay showed that the A value of the cells treated with AFG₁ at 2 000 μg/L was higher than that of the control. Double antibody sandwich enzyme linked immunosorbent assay (ELISA) results showed that AFG₁ at a dose of 100 μg/L could significantly inhibit lipopolysaccharide-induced TNF-α secretion.CONCLUSION: AFG₁ could stimulate the proliferation of HPBM and could decrease TNF-α secretion at certain concentration.     

Fasudil reduces formation of urethral stricture after injury via inhibiting Rho/ROCK pathway activation in rabbit urethra fibroblasts

AIM: To investigate the role of Rho-associated kinase (ROCK) inhibitor fasudil in the formation of rabbit urethral stricture after injury and to observe the cell activity, migration and extracellular matrix synthesis in the rabbit urethra fibroblasts. METHODS: The rabbit model of urethral stricture was established by microsurgical techniques. The rabbits were divided into sham operation group, operation group and fasudil (3 mg/kg, 10 mg/kg, 30 mg/kg) groups. The diameter of the stenosis was measured by retrograde urethrography 3 months after surgery. The fibroblasts were isolated from urethral scar, and then incubated with fasudil (12.5 μmol/L, 25 μmol/L, 50 μmol/L) in the presence of transforming growth factor-β1 (TGF-β1, 10 μg/L). The untreated cells were used for control. The cell activity was measured by MTT assay. The cell migration ability was tested by the method of Transwell chambers. The protein expression of ROCK, α-smooth muscle actin (α-SMA), collagen I and collagen III was determined by Western blot analysis. RESULTS: Fasudil significantly reduced formation of urethral stricture after injury (P<0.05). Cultured rabbit fibroblasts with different concentrations of fasudil inhibited the cell activity and cell migration ability (P<0.05). The protein expression of ROCK, α-SMA, collagen I and collagen III was also inhibited by treatment with fasudil in a dose-dependent manner (P<0.05). CONCLUSION: Fasudil inhibits the formation of extracellular matrix and reduces the incidence of urethral stricture after injury by down-regulating TGF-β1-induced Rho/ROCK pathway activation in the rabbit urethra fibroblasts.     

Effect of lipopolysaccharide on viability and secretion function of human umbilical vein endothelial cells

AIM: To observe the direct effect of lipopolysaccharide (LPS) on secretion of endothelin-1 (ET-1) and nitric oxide by human umbilical vein endothelial cell and cell viability of the secretor. METHODS: The third passage of human umbilical vein endothelial cells were incubated with different concentrations of LPS (1 g/L, 100 mg/L, 10 mg/L, 1 mg/L, 100 μg/L, 10 μg/L, 1 μg/L) for 6 hours, and the culture supernatants were collected. The concentrations of ET-1 were determined by radioimmunoassay, the concentrations of nitric oxide were determined using Greiss's method. The viabilities of cells were measured by MTT method. RESULTS: The concentration of ET-1 (pg/L) of normal control group was 251.64±10.90. The concentrations of ET-1 (pg/L) of LPS treated groups were 220.85±19.14, 278.67±15.45, 306.40±11.60, 312.87±33.50, 324.38±17.02, 291.49±14.30, 282.11±13.38, respectively (each group compared with normal control group, P<0.05 or P<0.01). The concentration of NO_x (μmol/L) of normal control group was 629.46±13.36. The concentrations of NO_x (μmol/L) of LPS treated groups were 732.58±23.21, 669.87±9.32, 661.24±16.80, 650.33±13.24, 606.59±12.94, 626.75±9.83, 627.61±5.61, respectively (each group compared with normal control group, P<0.05 or P<0.01). The viabilities of endothelial cells of LPS treated groups were 74%, 81%, 86%, 88%,91%, 93%, 93%, respectively. CONCLUSION: LPS of lower concentrations had no significantly lethal effect on human umbilical vein endothelial cells, but enhanced secretion of ET-1 and inhibited NO production. LPS in higher concentrations showed significant lethal effect on human umbilical vein endothelial cells, inhibited secretion of ET-1 and enhanced NO production.     

Effect of parthenolide on neointimal hyperplasia after balloon injury

AIM: To detect the effect and underlying mechanism of parthenolide (PN) on neointimal hyperplasia. METHODS: After 1 week of high-fat feeding, 30 male New Zealand white rabbits (2.0~2.3 kg) were randomly divided into 6 groups: sham+NS, rabbits received 0.9% normal saline after sham operation; sham+DMSO, rabbits received DMSO after sham operation; balloon injury(BI)+NS, rabbits received NS after balloon injury; BI+DMSO, rabbits received DMSO after balloon injury; BI+PN low, rabbits received PN at 1 mg/kg after balloon injury; BI+PN high, rabbits received PN at 2 mg/kg after balloon injury. The drugs were intraperitoneal injected once a day after the operation until sacrifice. After fed with high-fat diet for 4 weeks, the intima-media thickness, the expression of caspase-1, IL-1β, the levels of IL-8, TC, TG, LDL and HDL in the serum were measured. RESULTS: Compared with sham+DMSO group, the thickness of intima, the amount of caspase-1, IL-1β and IL-8 in BI+DMSO group were significantly increased (P<0.05). The levels of caspase-1, IL-1β and IL-8 were significantly decreased in BI+PN high group compared with BI+DMSO group (P<0.05). CONCLUSION: Neointimal hyperplasia is suppressed by PN after balloon injury, the potential mechanism may be associated with its anti-inflammatory role.     

Effect and mechanism of Qing-Kai-Ling on endotoxin-induced fever in rabbits

AIM:To explore the antipyretic mechanism of Qing Kai-Ling (QKL) injection on endotoxin (ET)-induced fever in rabbits.METHODS:Rabbit models of endotoxin (ET)-induced fever were duplicated. The rectal temperature was measured by digital thermograph. The cAMP and IL-1β content in the hypothalamus (HP), the cAMP content in the cerebrospinal fluid (CSF), and the arginine vasopressin (AVP) content in the ventral septal area (VSA) were determined by radioimmunoassay.RESULTS:① QKL had significant antipyretic effect on ET-induced fever(P<0.01), ② The production of IL-1β and cAMP in HP was significantly inhibited by QKL treatment (P<0.01), ③ QKL markedly decreased the cAMP content in the CSF and AVP content in the VSA(P<0.01).CONCLUSION:The antipyretic mechanisms of QKL are probably due to inhibiting the production of the endogenous pyrogen and central mediator of fever, and meanwhile stimulating the release of the antipyretic substances.