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Effect of Bupleurum Smithii on Complement and Rat Acute Lung Injury

Author: GuoLi
Tutor: ZhangYunYi；WengHongBo；LiHong
School: Fudan University
Course: Pharmacology
Keywords: Lobular black Bupleurum Complement hemolytic experiments Acute lung injury
CLC: R285
Type: Master's thesis
Year: 2008
Downloads: 198
Quote: 0
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Abstract

The complement system is an important part of one of the body's non-specific immune system plays an important role in the body's defense mechanisms, regulation of immune function and immune pathological process. The complement system is also important mediators of inflammation, abnormal activation serious pathological damage caused by the body's own tissues. Acute lung injury (acute lung injury, ALI) / acute respiratory distress syndrome (acute respiratory distresssyndrome, ARDS) is the more common clinical emergency and severe, patients often result in death due to acute hypoxic respiratory insufficiency or failure. Studies have shown that the activation of the complement system is associated with the development of the disease process. Bupleurum is a commonly used Chinese medicine for the treatment of inflammatory diseases and autoimmune diseases, the lobular black Bupleurum (Bupleurum smithii, B.smithii), roots in traditional Chinese medicine as Bupleurum use. Previous experiments had shown that Bupleurum has anti-complement hemolysis, but still have questions about the sites of action of the drug. The in vivo experiments also show that Bupleurum on acute respiratory distress syndrome model has a protective effect, but there is no direct evidence that Bupleurum in vivo by inhibition of the complement system arising from the role. The subject adopts hemolysis by observing the classic complement activation pathway and bypass the activation pathway Chinese medicine inhibiting hemolysis, to confirm the sites of action of Bupleurum and existing models of rat lung tissue sections were stained to determine whether the presence of complement deposition, then the model is improved, increasing blood gas analysis to refine the model, and provide guidance for future experiments. The first part of Bupleurum polysaccharides on inhibition of the complement system purpose study of Bupleurum total polysaccharides on the role of the complement system. Bupleurum total polysaccharides were mixed with some elements of the complement hemolytic experiments, for a period of time before adding other components, observing system hemolytic explore the role of the classical pathway or the alternative pathway of complement activation. Results in the classic activation pathway, Bupleurum the total polysaccharides with complement pre-mixed, can reduce the system's final hemolytic hemolysin or sheep erythrocytes hemolysis of pre-mixed system did not change significantly. Bypass activation pathway, Bupleurum total polysaccharide complement premixed can reduce system ultimate hemolytic, pre-mixed system with rabbit erythrocyte hemolysis did not change significantly. Conclusions the Bupleurum total polysaccharide by inhibiting complement, the impact of hemolysis. The second part of acute lung injury in complement establish a rat model of ALI purpose of the deposition in the lung tissue, the protective effect observed complement deposition, and Bupleurum total polysaccharides of the lung tissue of animals. Method by ischemia and reperfusion and airway instillation of endotoxin establish two combat rat model of ALI, monitoring of serum total complement activity and blood CO ₂ concentration changes by HE staining and immunohistochemical method to observe the the animals lung tissue lesions and complement C3c deposition. Results with the sham surgery group blood samples CO ₂ concentration increased complement activity decreased slightly compared with the model group and the negative control group blood samples CO ₂ concentration have risen significantly complement activity declined slightly, while the of Bupleurum group and positive drug group blood samples CO ₂ concentration increase is relatively small, a significant decline in the activity of the complement. HE staining showed pseudo-operation group of the lungs of animals almost no damage, the model and the serious injury of the lungs of animals of the negative control group, while the of Bupleurum group and positive drug group animal lung injury lighter. Immunohistochemistry results also show that the model group and negative control group animals lung of complement C3c deposition the Bupleurum group, positive drug group and sham surgery group animals the lungs basic look less than complement deposition. Conclusion Bupleurum polysaccharides in vivo inhibition of complement can improve ischemia reperfusion and endotoxin-induced lung inflammation, relieve rat ALI, accompanied by a significant reduction in lung tissue deposition of complement. Model of acute lung injury in the third part of the problem is to explore the purpose of improvement of the existing rat model of ALI to explore the problems encountered in the modeling process. By ischemia-reperfusion and airway instillation of endotoxin to establish two-hit rat model of ALI, Determination of serum complement hemolytic activity, and arterial oxygen pressure was measured two ways (the PaO ₂ ) and partial pressure of carbon dioxide (PaCO ₂) changes. Results model, compared with the normal control group, PaO _{, 2} sham operation group and normal control group with modeling time significantly decreased, PaCO ₂ increased, blood gas analysis comparable. Using automatic blood gas analyzer values ??than the laboratory determined using the corresponding oxygen electrode and the carbon dioxide electrode is more reasonable, accurate and high precision. Complement hemolytic activity results show that the normal control group remained at a high level, the model complement activity decreased with time, pseudo-operation group and normal control group at 2h equivalent in 4h decreased. Conclusions in a rat model of ALI should fully automated blood gas analyzer PaO ₂ and PaCO ₂, the research complement activation, control modeling in 4h avoid non-ALI / ARDS reason caused complement activation.

Effect of Bupleurum Smithii on Complement and Rat Acute Lung Injury

Abstract

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