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Effects of Bupleurum Smithii on Macrophage Immunomodulatory Activity in Mice and on Acute Lung Injury in Rats

Author: ChengXiaoQin
Tutor: LiHong；ZhangYunYi
School: Fudan University
Course: Pharmacology
Keywords: Lobular black Bupleurum Macrophages Swallow Acute lung injury Cytokines Complement
CLC: R285.5
Type: Master's thesis
Year: 2010
Downloads: 161
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Abstract

Systemic lupus erythematosus (SLE) and acute lung injury / acute respiratory distress syndrome (ALI / ARDS) is a common clinical two diseases. SLE is a multisystem autoimmune disease, clinical manifestations of complex, prolonged course repeatedly, the patient is often accompanied by a variety of abnormal autoantibodies and complement activation, the majority of patients ultimately renal insufficiency, severe impact on the lives of patients. ALI / ARDS is a severe infection, shock, trauma and burns, non-cardiac disease process, pulmonary capillary endothelial cells and alveolar epithelial cell damage caused by diffuse pulmonary interstitial and alveolar edema caused by acute hypoxic respiratory function insufficiency or failure. Both diseases have in common to a certain extent. Within First, both are included in the autoimmune diseases, immune function disorders; second, non-specific immune responses play an important role in the disease process associated with. Third, both the progression there is a massive release of inflammatory cytokines. Bupleurum traditional Chinese medicine in China and commonly used in traditional Chinese medicine, including perennial herb Umbelliferae the Bupleurum (North Chaihu) Bupleurum chinensis DC angustifolia Bupleurum (South Chaihu) Bupleurum scorzonerifolium Willd has anti-inflammatory and immunomodulatory the role. The lobular the black Bupleurum distribution in Northwest China in past studies, we extracted from lobular black Bupleurum roots of Bupleurum polysaccharides, and confirmed that (1) lobular black Bupleurum polysaccharides (BPs) of Campylobacter jejuni CJ- S131 induced systemic lupus erythematosus (SLE)-like mice better preventive and therapeutic effects: inhibition of SLE humoral immune hyperthyroidism, inhibited splenomegaly and relieve kidney injury; (2) in the ALI rat model , the preliminary observation to lobular black Bupleurum total polysaccharide 10 mg · kg-1 can alleviate ALI pathological damage, and can inhibit excessive complement activation and reduce the deposition of complement activation products in the lung tissue. In view of the above we already pharmacodynamic research, combined with the monocyte-macrophage system played an important role in both diseases, we observed Bupleurum polysaccharides on macrophages mouse monocyte-macrophage system the role, to further understanding of the possible targets of Bupleurum polysaccharides on the role of SLE; observe the Bupleurum total polysaccharides its specific mechanisms of the protective effect in acute lung injury model. Objective To study the role of regulation by a the Bupleurum total polysaccharide of murine macrophage immune function lobular black Bupleurum polysaccharides on mouse peritoneal macrophage function. Methods Mice were randomized, the lobular black Chaihu total polysaccharides (BPs20, 40,80 mg · kg-1 · d-1), prednisone acetate of (Prednisone 3 mg · kg-1 · d-1) or levamisole ( Levamisole 25 mg · kg-1 · d-1) ig (day 0-day 6), observed a the lobular black Bupleurum polysaccharides on mouse peritoneal macrophage function. Detection include the detection of drugs on the mercapto ethanol in mice induced by sodium-activated macrophage phagocytosis itself apoptotic cells, antibody-mediated sheep red blood cells (SRBC) and chicken erythrocytes (CRBC) function; Griess method detects drugs of mercapto ethanol sodium-induced activation of macrophages and bacterial lipopolysaccharide (LPS)-induced inflammatory macrophage culture supernatant of the influence of nitric oxide (NO) levels; ELISA assay of drugs on the activation and inflammatory macrophage culture supernatant levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin -6 (IL-6). Results Bupleurum 80 mg · kg-1 · d-1 increased their apoptotic cells activated macrophages phagocytic percentage and phagocytic index (P lt; 0.001, P lt; 0.01). Bupleurum 20, 40 and 80 mg · kg-1 · d-1 significantly increased sheep red blood cells to antibody-mediated activation of macrophages, phagocytic percentage and phagocytic index (P lt; 0.001); promote the activated macrophages The phagocytic percentage chicken erythrocytes (P lt; 0.05) and phagocytic index (P lt; 0.01). Bupleurum 20, 40, and 80 mg · kg-1 · d-1 significantly inhibited the activation of macrophages secrete NO and IL-6 levels (P lt; 0.001), activated macrophages secrete TNF-α and IL no impact;-1β levels compared with the activation of macrophages, LPS-stimulated inflammatory macrophages to secrete NO, TNF-α and IL-1β levels were significantly higher (P lt; 0.01). Bupleurum 40,80 mg · kg-1 · d-1, significantly reduced inflammatory macrophage secretion of NO, TNF-α and IL-1β levels (P lt; 0.001). The Bupleurum 20,40,80 mg · kg-1 · d-1 reduces the level of inflammatory macrophages to secrete IL-6 (P lt; 0.001). Conclusion regulatory role: to promote the phagocytic activity of mouse peritoneal macrophages (phagocytic autoantigen, phagocytosis of IgG opsonized sheep red blood cells, phagocytosis of chicken erythrocytes); Bupleurum polysaccharides on function of mouse peritoneal macrophages activated macrophages cells release cytokines lighter, but excessive NO release inflammatory macrophages, TNF-α, IL-1β and IL-6 was significantly inhibited. The 2 the Bupleurum total polysaccharide of acute lung injury, the role of the purpose of research lobular the black Chaihu total polysaccharide protective effects and mechanisms of acute lung injury. Rats were randomly divided into sham operation group (sham), made module (model) Bupleurum group (BPs 2.5, 5, 10, 20 mg · kg-1, ig) and positive control group (dexamethasone phosphate sodium, dexamethasone 2 mg · kg-1, ip). By ischemia and reperfusion and endotoxin airway infusion rat model of ALI. Lung tissue for biopsy, HE staining observed the rat lesions and administration to improve the situation; determination of rat lung wet-dry weight ratio; Determination of alveolar bronchoalveolar lavage fluid (BALF) protein content in Coomassie blue; counting BALF of neutral granulocyte content; determination BALF MPO content; the ELISA assay BALF cytokines IL-6, and TNF-α content; determination of total serum complement levels hemolysis. Ischemia and reperfusion and LPS infusion can be successfully induced acute lung injury model. Compared with the sham surgery group, the model group were significant lung damage, pathological visible heavy bleeding, thickening of the alveolar walls and alveolar deformation collapse; lung wet to dry weight ratio, neutrophil count in BALF of liquid protein, MPO, The content of TNF-α, IL-6 and serum total complement activity has significantly increased (P lt; 0.001). After oral administration, Bupleurum significant improvement in the pathological damage, biopsy show administration significantly reduced the degree of inflammation, significantly reduced alveolar hemorrhage, alveolar wall thinning, reduce inflammatory cell infiltration. Bupleurum 10 and 20 mg kg-1 significantly reduced the ratio of wet to dry weight (P lt; 0.05). Bupleurum each dose group BALF protein and TNF-α levels significantly decreased (P lt; 0.01); the Bupleurum 5,10 and 20 mg · kg-1 reduced the number of BALF neutrophils, inhibition of MPO and IL-6 levels higher (P lt; 0.001); Bupleurum 20 mg · kg-1 reduced the level of serum complement classical pathway activation. (P lt; 0.05). Conclusion by ischemia and reperfusion and LPS instillation can be successfully induced acute lung injury model. The administration lobular black Bupleurum polysaccharide significant improvement of lung injury, reduce the high permeability of the alveolar epithelial and endothelial cells to improve alveolar space and pulmonary interstitial edema and reduced neutrophil aggregation infiltration, its mechanism of action can be inhibiting the release of inflammatory cytokines and excessive complement activation.

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