ABSTRACT
Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR). It has 31 amino acid residues; SLN and phopholamban (PLB) are belong to the same protein family, so they have similar physiological functions. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure. However, much remains to be elucidated. SLN independently or in conjunction with PLB affects SERCA activity, imbalancing intracellular calcium homeostasis, and reducing myocardial contractivity; these effects promote the development of heart failure.
Subject(s)
Animals , Humans , Calcium-Binding Proteins , Physiology , Heart Failure , Muscle Proteins , Metabolism , Physiology , Myocardial Contraction , Physiology , Proteolipids , Metabolism , Physiology , Sarcoplasmic Reticulum , Metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases , MetabolismABSTRACT
Objective Tostudy the effects ofRheu compositus (Dachengqi Decoction, DD) on the NF-κBactivity of alveolar macrophages in ARDS rats and its inflammatory cytokine expression, and hence to explore the molecular mechanism of the anti-inflammatory effects of DD. Method The 65 male Wistar rats were randomly di-vided into the control group (n = 12), the ARDS model group (n = 21), the DD treatment group (n = 16) and the dexamethasone treatment group (n = 16). The rots of model group received 1 mg/(kg·0.5 mL) LPS injected intra-poritoneally and LPS in dose of 5 mg/(kg·0. 5 mL) was administrated by slow dropping endotracbeally 16 hours later. Modeling was successfully established 6 hours later evidenced by arterial gas analysis. The rats of con-trol group received 0.5 mL normal saline injected intravenously through tail vein instead of LPS. Three days after establishment of modeling, DD was given to rats of DD treatment group by intragastric instillation for 3 days in dose of 2.31 g/(kg·d),in which the weight of drug was calculated on the basis of dried herbal medicine. In dexam-ethasone treatment group, rats had intra-peritoneal injection of 2 mg/kg dexamethasone for 3 days after modeling was established. Seventy-two hours later, the arterial blood gas analysis and pathological study were carried out, in rats of all groups, and the findings were graded. The levels of TNF-α, IL-1 and IL-10 both in the plasma and in the brenchoalveolar lavage fluid were determined by using the enzyme linked immunosorbent assay (ELISA). Besides the nucleopretein concentration of pulmonary alveolar macrophage (PAM) was maeasuredwith the BAC method, and the NF-κB activity was determined with the Western Blotting, and with the evaluation of the DD' s effect on the transcription activity of PAM inflammatory cytokines. All the experimental data were processed by the SPSS 13.0 for statistical analysis. The analysis of variance was used for the comparison between groups, and P < 0. 05 showed the statistical significance of the difference. Results DD didn' t significantly reduce the TNF-α level [(510.97±76.20) pg/mL,(476.16±98.03) pg/mL, P >0.05], but significantly deceased the plasma IL-1 level [(381.99±34.30) pg/mL, (300.69 ± 50.99) pg/mL, P <0.05]. At the same time, there was no signif-icant changes in the plasma IL-10 level [(345.96 ± 67.72) pg/mL, (345.30 ± 78.52) pg/mL, P > 0.05]. Whereas TNF-α level in BALF was significantly decreased [(130.94 ± 33.51) pg/mL, (106.59 ± 26.64) pg/ mL, P < 0. 05, so was the IL-1 level in BALF (82.5 ± 25.36) pg/mL, (63.89 ± 22.96) pg/mL, P < 0. 05], but IL-10 level in the BALF was significantly increased[(77.09 ± 26.05) pg/mL, (148.05 ± 53.50) pg/mL, P <0.01]. DD significantly reduced the nueleoprotein level of PAM[(5.35 ± 2.44) μg/μL, (3.54 ± 2.01) μg/ μL, P < 0.05]and significantly inhibited the NF-κB activity [electrophoretic band optical density × area/consult mtio:(1.45±0.71),(1.11±0.28), P <0.05]aswell. Conclusions DD regulated systemic pro-inflammato-ry media/anti-inflammatory media balance in rats with ARDS by mainly reducing the level of IL-1. The regulatory effects of DD on the local lung injury not only inhibit the producing of TNF-α and IL-1 level,but also increase the IL-10 level to reestablish the local pro-inflammatory factors/anti-inflammatory factors balance so as to inhibit the lo-cal excessive irranune response. DD inhibits the NF-κB activity in the PAM of ARDS rats so as to restrain the pro-duction of pro-inflammatory cytokines (TNF-α and IL-1). This kind of multi-target bidirectional regulation plays an active role in regulating the immune balance and protecting the target organ from the excessive injury.
ABSTRACT
To establish a stable and reliable model of refractory hypoxemia acute respiratory distress syndrome (ARDS) and examine its pathological mechanisms, a total of 144 healthy male Wistar rats were randomized into 4 groups: group I (saline control group), group II (LPS intravenous "single-hit" group), group III (LPS intratracheal "single-hit" group) and Group IV (LPS "two-hit" group). Rats were intravenously injected or intratracheally instilled with a large dose of LPS (10 mg/kg in 0.5 mL) to simulate a single attack of ARDS, or intraperitoneally injected with a small dose of LPS (1 mg/kg) followed by tracheal instillation with median dose of LPS (5 mg/kg) to establish a "two-hit" model. Rats in each group were monitored by arterial blood gas analysis and visual inspection for three consecutive days. Arterial blood gas values, lung wet/dry weight ratio and pathological pulmonary changes were analyzed to determine the effects of each ALI/ARDS model. Concentrations of TNF-alpha, IL-1 and IL-10 in the bronchoalveolar lavage fluid (BALF) and blood plasma were measured by using enzyme-linked immunosorbent assays (ELISA). Our resulsts showed that single LPS-stimulation, whether through intravenous injection or tracheal instillation, could only induce ALI and temporary hypoxemia in rats. A two-hit LPS stimulation induces prolonged hypoxemia and specific pulmonary injury in rats, and is therefore a more ideal approximation of ARDS in the animal model. The pathogenesis of LPS two-hit-induced ARDS is associated with an uncontrolled systemic inflammatory response and inflammatory injury. It is concluded that the rat ARDS model produced by our LPS two-hit method is more stable and reliable than previous models, and closer to the diagnostic criteria of ARDS, and better mimics the pathological process of ARDS.
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Objective To illustrate the effect of Madopar on nerve cell apoptosis of rats with Parkinson’s disease (PD). Methods Hemi-lateral PD model was made by injecting 6-OHDA into the black substance of the right side of the brain and treated with Madopar. At the same time,the normal group and sham-operation group were set up,and TUNEL staining and transmission electro-speculum were employed to observe the apoptosis of nerve cells. Results The TUNEL positive cells(23.50?3.85) were significantly less than the model group(37.83?6.46) and the comparison of apoptosis cells counting showed marked difference( P
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OBJECTIVE: To observe the effect of Chinese and western medicine integration on the spinning behavior of rats with Parkinson disease. METHODS: Model of the lateral Parkinson disease was made with injection of 6-hydroxydopamine (6-OHDA) into the black substance of the right side of the brain, and the model rats were treated with madopar and Chinese herbs for nourishing the liver and kidney, clearing collaterals and detoxification. The rat's spinning behavior was observed, and was compared with the normal control group, madopar group and sham-operation group at the same time. RESULTS: Chinese and western medicine integration could obviously reduce the spinning circles of the rats. CONCLUSION: Chinese and western medicine integration can significantly improve the spinning behavior of the model rats.
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AIM:To investigate the effect of Dachengqi decoction(DD)on the acute respiratory distress syndrome(ARDS)in rat model induced by endotoxin "two-hit".METHODS:48 healthy male Wistar rats were randomly divided into 4 groups:control group,ARDS model group,ARDS+DD treatment group and ARDS+dexamethasone treatment group(12 in each group).E.coli lipopolysaccharide(LPS)"two-hit" induced ARDS model in rats was established.The arterial blood gas analysis,lung wet/dry weight(W/D)ratio and lung tissue pathology observation and scoring were measured to evaluate the pharmacological effects of DD on ARDS.The levels of TNF-?,IL-1 and IL-10 were determined by ELISA to explore the immune regulatory mechanism of DD.RESULTS:(1)Treatment with DD significantly improved blood pressure in rats,increased oxygen saturation,decreased lung wet/dry weight ratio and lung injury score,relieved pulmonary edema and the inflammatory responses.(2)DD suppressed the productions of systemic and pulmonary pro-inflammatory mediators and promoted the release of anti-inflammatory mediators in lung.CONCLUSION:The inhibitory effects of DD treatment on pulmonary inflammatory response are not only related to reducing the extent of systemic inflammatory response,but also promote pulmonary anti-inflammatory production and regulate the balance of pulmonary pro-inflammatory mediators and anti-inflammatory cytokines.This specific regulatory effect protects the target organ from excessive inflammatory organ injury,discloses that DD has advantages in the treatment of endotoxic ARDS.
ABSTRACT
Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS),the complicated and devastating illness,resulted from various processes of systemic inflammatory response syndrome(SIRS),injure directly or indirectly the lung.With the advance of investigations in SIRS and multiple organs disfunction syndrome(MODS),inflammation development and control have been considered to be the important mechanism of ALI/ARDS.The research hotspot is also focused on the inflammatory cells and cytokines.Dachengqi decoction can influence on the functions of inflammatory cells and cytokines,so the strategies of anti-inflammatory treatment on immunoregulation became the key point for prevention and treatment of ALI/ARDS with traditional Chinese medicine.