CN1393250A - Aqueous extract of sapanwood for treating acute rejection reaction after organ transplantation - Google Patents
Aqueous extract of sapanwood for treating acute rejection reaction after organ transplantation Download PDFInfo
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- CN1393250A CN1393250A CN 01127907 CN01127907A CN1393250A CN 1393250 A CN1393250 A CN 1393250A CN 01127907 CN01127907 CN 01127907 CN 01127907 A CN01127907 A CN 01127907A CN 1393250 A CN1393250 A CN 1393250A
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Abstract
A novel application of the aqueous extract of sapanwood in treating the acute rejection reaction after organ transplantation is disclosed. Its advantages are high effect, low cost and low toxic by-effect.
Description
The present invention relates to a kind of single medicinal material that is used for anti-organ transplantation acute rejection---aqueous extract of lignum sappan.
Late period or latter stage at end, the patient was when using conventional Therapeutic Method invalid, and adopting organ transplantation is unique efficient ways.Through countries in the world scholar's hardships research and positive clinical practice in the last hundred years, cardiac transplantation of the same race is increasingly mature, thereby makes ten hundreds of patients obtain new life.From present level of development, the success of organ transplantation and the length of time-to-live are with all multifactor relevant.Except that the technology that possesses essential equipment and exquisiteness, postoperative is monitored timely, is diagnosed rejection and treats also very important.
Chemical immunosuppressant has played pivotal role in the prevention of organ transplantation acute rejection and treatment, and has promoted the development of heart transplantation.Yet, do not reach satisfied effect.Up to now, all right and wrong are special to be applied to each clinical chemical immunosuppressant, they can reduce receptor's general immunity function, thereby reduce resistivity to infection and tumor, and medicine also has certain toxic and side effects, if can not tolerate, usually be forced to drug withdrawal, thereby influence the long-term surviving of graft.In addition, resemble the such medicine of CsA (cyclosporin A), cost an arm and a leg, also make the receptor be difficult to bear.Therefore, the problem that seek effectively, low toxic and side effects and cheap immunosuppressant has become the present common concern of medical circle.In recent years, people recognize that progressively the medicine of seeking the anti-rejection make new advances from Chinese medicine may be a new way full of hope, and it is light that Chinese medicine has toxic and side effects, lower-price characteristic.In recent years, use single medicinal material antagonism immunologic rejection and carried out number of research projects, the medicine of anti-immunologic rejection has following two kinds to find to have clearly:
1, Tripterygium glycosides.Immunity of Tripterygium glycosides pair cell and humoral immunization all have inhibitory action.It can obviously prolong the survival of mouse skin, heart and rat heart alloplast, clinical renal homotransplantation Preliminary Applications result shows, Tripterygium glycosides can replace azathioprine and ciclosporin A drug combination, but the toxic and side effects of Tripterygium glycosides mainly is gastrointestinal reaction, leukopenia, thrombocytopenia, patient's male oligospermia, symptoms such as weak, drowsiness and headache can appear in a few patients, and some toxic and side effects waits further further investigation.If as routine administration, also need the further chemical constitution of research active ingredient, and purified, separate.
2, Cordyceps.People have studied its pharmacological action widely, owing to find the method difference that Cordyceps extracts, demonstrate different pharmacological actions, therefore, are applied to organ transplantation and still need and do a large amount of work.
The purpose of this invention is to provide the single medicinal material that is used for anti-organ transplantation acute rejection---the aqueous extract of lignum sappan that a kind of toxic and side effects is little, cheap, can be used as routine administration.
Technical scheme of the present invention:
The present invention is a kind of new purposes of aqueous extract of lignum sappan, is the medicine that aqueous extract of lignum sappan is used as anti-organ transplantation acute rejection.
To motherland's medical science, anti-organ transplantation immunologic rejection is a new problem, in acute rejection graft be ostracised occur around the vascular endothelial cell swelling and degeneration, blood vessel often around inflammatory cell infiltration, edema, hemorrhage, infringement of a series of small vessel diseases reason and microcirculation disturbance such as little vascular wall thickens, luminal stenosis even thrombosis." congestion " in this pathological changes and the motherland theory of medicine is comparatively similar.Studies show that, activating blood and removing stasis drug has the cell of alleviating and hematoblastic gathering, adjust the disorder of blood vessel wall permeability, blood vessel dilating, adjust blood viscosity, effects such as anti-hemostasis-coagulation and promotion fibrinolytic, thereby can improve the graft microcirculation disturbance that rejection causes, the survival period of graft is prolonged.In addition.Activating blood and removing stasis drug can suppress body and produce antibody.Obviously, immunosuppressive action is one of reason of these medicines prolongation graft survivals.The present invention can prolong the time-to-live of heart transplant, alleviate rejection with the immunologic injury due to the organ, and toxic and side effects is little, and is cheap.
Be animal experimental data below:
The foundation of model and grouping:
Laboratory animal: the Wistar rat, male, 160-200g, the SD rat, male, body weight 200-250g.All available from Beijing Medical University's Experimental Animal Center.
Key instrument: SXP-1B type operating double binocular microscope, optical instrument factory, Shanghai; SSW-3 type microsurgical instruments set, Shanghai Medical Instruments factory; Constant water bath box, Shanghai Medical Instruments factory.
Experimental drug:
Cyclosporine A: sandimmun neoral (Sandoz Pharma Ltd. produces, and every contains CsA25mg) is dissolved in normal saline, is diluted to 1mg/ml concentration, 4 ℃ of preservations are standby.
The preparation of Lignum Sappan water extract: Lignum Sappan, available from Heilongjiang Province's medical material company, identify through crude drug in Yunnan, the place of production.Soak after 1 hour, decocting three times, each 40min, decocting liquid mix the back water-bath and are condensed into 1.75g/ml concentration for 80 ℃, and 4 ℃ of preservations are standby.
Supply anxious get art and receptor operation.
Experiment grouping and processing: clear-headed (about 2h) can stand with postoperative, transplants heart beating strong (supplying heart beating heart in the 24h) person, as the animal for research model.Above-mentioned rat is divided into four groups at random, 5 every group.First group is model control group, except that normal nursing, gavages with the volume normal saline.Second group of cyclosporin A group behind the 24h of operation back, gavages the cyclosporin A solution for preparing, and presses the 40mg/kg administration.The 3rd group is the Lignum Sappan group, behind postoperative 24h, gavages aqueous extract of lignum sappan, presses the 17.5g/kg administration.The 4th group is SD matched group (the SD rat is respectively donor, receptor), and operation back 24h gives the normal saline with volume, gavage 11 continuously after, put to death animal respectively.
The result:
Each treated animal is after surgery behind the 24h, and diet, drinking-water are more normal, and behind the about 3-4d of postoperative, wound healing is good.The experiment contrast group is grown better, and fur is glossy, and it is transplanted the heart and generally stops to fight about 5-7d.The Lignum Sappan group is grown more normal, and fur is glossy, when 11d, still can touch its heartbeat.The cyclosporine A group is grown relatively poor, and diet is less, and fur is gloss not, and it transplants the heart when 11d, still can touch heartbeat.
PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM:
As seen the experiment contrast group is transplanted the heart and is wrapped up by abdominal tissue fully, can't see heartbeat.The heart enlargement, be graniphyric, the visible heart wall of ventricular muscles tangent plane thickens, loose, subregion is canescence.Visible myocardial cell edema is more obvious under the light microscopic low power, and sees that lamellar is arranged is hemorrhage and downright bad.Visible on every side a large amount of cell infiltration, a spot of myocardial cell fiber.As seen the diffusivity edema is arranged, a large amount of cell infiltration and a spot of myocardial cell, most of myocardial fibrosis, and visible hemosiderin and hemorrhage under the high power lens.Under high power lens (400 *), as seen a large amount of mononuclearcells soaks into, as seen a small amount of cardiac muscle fiber, the swelling of part myocardial cell, vacuolar degeneration, can have only cardiac muscle dissolving, fibroblast proliferation and gtelatinous fibre form, and change such as fibrosis, visible vessels expansion simultaneously, the myocardial cell disintegrate becomes fine grained.
The heart surface of Lignum Sappan group smooth ruddy, do not have the parcel phenomenon at intraperitoneal, heart beating is beaten effectively.Whole pathological changes is lighter under the low power lens, and as seen diffuse cell infiltration is arranged, the degeneration of part myocardial cell, visible on every side edema.Accidental myocardial cell granular degeneration under the high power lens, and as seen band is still arranged, a matter is seen a small amount of monokaryon, lymphocytic infiltration, and edema is lighter.
Smooth ruddy, the nothing parcel of CsA group heart surface, heartbeat is strong.Can see that the focal inflammation cellular infiltration is arranged at subintima under the low power lens, not have obvious edema on every side.Seeing under endocardium under the high power lens has special mess shape cell infiltration, and adventitia is seen a small amount of lymphocytic infiltration, and myocardial cell changes not obvious.
The SD group changes lighter, smooth surface, nothing parcel, and heartbeat is strong, and as seen a small amount of cell infiltration is arranged under the low power lens, and myocardial cell is not seen obvious change, and not seeing on every side has edema.The visible vessels wall is normal under the high power lens, and cardiac muscle has cell infiltration on every side, and not seeing has myocardial cell degeneration, necrosis.
Ultrastructural change:
Under the cardiac muscle transmission electron microscope, as seen model group has a large amount of inflammatory cells, and the nucleus naivety is mainly lymphocyte, plasma cell, granulocyte etc., and see that a matter is arranged is hemorrhage, the myocardial cell mitochondrial vacuolar degeneration is more obvious, myofilament capsule vacuolar degeneration, the part myofilament is arranged loose, fracture, and the profit dish is relatively poor to educate.
Lignum Sappan is organized visible myocardial cell and physically well develops, and the visible a large amount of inflammatory cells of a matter are many with lymphocyte, plasma cell, and structure of mitochondria physically well develops.A large amount of pinosomes and matter shape projection are arranged in the vascular endothelial cell.
CsA organizes visible less inflammatory cell, and cardiac muscle fiber Z line two ends light and shade band is clearer, and mitochondrion physically well develops, and does not see disorderly shape degeneration and fracture, and vascular endothelial cell physically well develops.
SD organizes that visible myocardial cell function is active, nucleus is more complete, cell infiltration is less, vascular endothelial cell, and mitochondrion physically well develops.
About heart transplantation acute rejection model:
The Rats of Allogeneic Transplantation model of relatively generally acknowledging has at present been adopted in this experiment, and this model is the abdominal ectopic heart transplantation model that OnoShi was founded in 1969.Though donor's heart does not have the function of heart itself, because the adequate blood supply is arranged, and can survive the regular hour, can the comparatively ideal animal model in aspect such as prevent and treat as the mechanism of research acute rejection and to it.
Morphological changes of various tissue components:
This laboratory observation to the result show, the transplanting heart of model group is generally in the time of 5-7 days, heartbeat touches not obvious, after treating to put to death animal in 11 days, visible down necrosis of myocardial cell occurrence of large-area and the myocardial fibrosis of transplanting the heart of light microscopic, the prompting rejection is heavier, the survival period of its heart transplant and bibliographical information mutually one to.This phase also can be found vascular endothelial injury simultaneously, and matter is bled profusely between cardiac muscle, and the immunoreation of prompting acute fluid has also participated in acute rejection, and it is similar that this result and human heart are transplanted the rejection that takes place.
The heart transplant of SD rat matched group, heartbeat is still stronger when putting to death, rarely seen infiltration that inflammatory cell is arranged under the light microscopic, cardiac muscle and blood vessel all do not take place obviously to change, point out between SD individuality of the same race and after the heart transplantation acute rejection does not take place, but because the process of operation also is the process of wound, so as seen to a certain degree inflammatory reaction is arranged.
The transplanting heart of CsA group is when putting to death, heartbeat is still strong, and smooth surface, pathological changes is lighter under the light microscopic, inflammatory cell and lymphocytic infiltration are arranged, but myocardial cell there is not tangible change, illustrates that CsA can obviously alleviate rejection, prolong the time-to-live of graft, can yet be regarded as and suppress a kind of good medicine of rejection at present.Yet the ordinary circumstance of animal performance is relatively poor, and visible CsA also is tangible to damage and the toxic and side effects of animal.
The transplanting heart of Lignum Sappan group in the time of 11 days, still visible strong heartbeat, and the surface is more smooth, does not have parcel.Though and light microscopic visible down obviously inflammatory cell and lymphocytic infiltration, myocardial cell degeneration and peripheral edema; and do not see the necrosis that myocardial cell is arranged; prompting Chinese medicine Lignum Sappan has certain inhibitory action to generation, the development of acute rejection, and myocardial damage is also had the certain protection effect.Simultaneously do not see that obvious toxic and side effects is arranged yet.
The variation of myocardial ultrastructure:
CsA can obviously suppress the myocardial damage due to the acute rejection, and humoral factor is also had certain inhibitory action.From the situation of the function of myocardial cell and mitochondrial growth and cell infiltration, also be confirmed, the Chinese medicine Lignum Sappan also can suppress immunological rejection to a certain extent, its myocardial cell and structure of mitochondria physically well develop, but as seen a matter has a large amount of inflammatory cells.From Ultrastructural angle, proved the anti-immunologic rejection effect of Lignum Sappan.
The expression of PEP mRNA changes:
When heart was transplanted back generation acute rejection, cytotoxic T cell was activated, assembles, and the PFP expression obviously raises.
Result from this research, without the cardiac muscular tissue of the model group of any processing, in the time of 11 days, the mRNA expression of its PFP obviously increases, match with myocardium pathomorphology and the Ultrastructural variation of the same period, the SD matched group is not seen the expression of the mRNA of obvious PFP.CsA can obviously suppress the mRNA expression of PFP, thereby suppresses acute rejection.
From the result of Lignum Sappan group, the mRNA expression of its PFP is starkly lower than model control group, but slightly high than the CsA group, shows that Lignum Sappan can suppress the expression of CTL cell PFP, has certain anti-immunologic rejection effect.
The expression of granule B (GraB) mRNA changes:
Recent study shows that granzyme is a kind of important effector molecule, and its cytotoxicity has been studied clearly.
This result of study shows that the mRNA expression of model group GraB obviously increases, and the SD matched group does not have obvious expression, and this has illustrated that also this experimental model is successful.The CsA group obviously alleviates with the mRNA expression of Lignum Sappan group GraB, has shown that CsA and Lignum Sappan have the downward modulation effect to the expression of GraB.
GraB and mRNA expression between Lignum Sappan group and the CsA group do not have significant difference.
The variation of peripheral blood IL-2 level:
From the result of this research, in the model group that acute rejection has taken place, IL-2 obviously raises, and illustrates that IL-2 has participated in rejection.And CsA lowers the level of IL-2, should reach and brings into play its immunosuppressive action thereby suppressed immunity.Lignum Sappan group IL-2 level also is starkly lower than model control group, the prompting Lignum Sappan is to the secretion of IL-2, certain inhibitory action is also arranged, and the generation of pair cell toxicity T cell (CTL) and maturation also have certain inhibitory action like this, thereby influence generation, the development of rejection.
The variation of all IL-6 levels of outer blood:
The result of this research shows that the IL-6 level of model group obviously increases, and SD matched group IL-6 level is lower, shows that IL-6 had participated in reaction wherein when acute rejection took place.CsA can obviously suppress the secretion of IL-6, thus generation, the development blocking or alleviate rejection.The IL-6 level of Lignum Sappan group also is starkly lower than model group, and the prompting Lignum Sappan can suppress the secretion of IL-6, thereby alleviates the damage that acute rejection brings.
CD4
+, CD8
+The variation of ratio:
This ratio of model group obviously raises in this research, and the ratio of CsA group and Lignum Sappan group is all lower, shows the equal regulating immunological function of CsA and Lignum Sappan, makes CD4
+/ CD8
+Ratio approach normal level, shown that Lignum Sappan and CsA have immunoregulation effect equally.
Cardiac cellular apoptosis: the result of study of this experiment shows that the model group apoptosis of cardiac muscle obviously strengthens, and the SD matched group only has the apoptosis of minute quantity, and CsA can obviously suppress cardiac cellular apoptosis.The apoptosis of cardiac muscle of Lignum Sappan group is obviously seen few, and the prompting Lignum Sappan can pass through to suppress cardiac cellular apoptosis, thereby alleviates acute rejection.
By this research, can draw as drawing a conclusion:
The Rats of Allogeneic Transplantation model is a comparatively ideal model of research heart transplantation acute rejection.Lignum Sappan has certain anti-immunologic rejection effect, can prolong the time-to-live of heart transplant, alleviates rejection to the immunologic injury due to the cardiac muscle.Lignum Sappan can suppress the expression that cardiac muscle soaks into the mRNA of cell perforation element, the mRNA of granzyme B is expressed also have certain inhibitory action, and can suppress the excessive apoptosis of myocardial cell.Lignum Sappan can be lowered the content of heart transplantation model peripheral blood IL-2, IL-6, regulates outside blood CD
+ 4/ CD
+ 6The disorder of ratio, thereby bring into play its immunosuppressive action.
In sum, Lignum Sappan has the anti-immunologic rejection effect of organ transplantation.
Embodiment:
The present invention is a kind of new purposes of aqueous extract of lignum sappan, is aqueous extract of lignum sappan is used for anti-organ transplantation acute rejection.Aqueous extract of lignum sappan can be a Lignum Sappan water extract, and preparation method is after Lignum Sappan is soaked 1 hour, decocting three times, and each 35-45min, decocting liquid mixing water-bath is condensed into 1.75g/ml concentration for 80-90 ℃, and 4 ℃ of preservations are standby.
Claims (1)
1, a kind of new purposes of aqueous extract of lignum sappan is characterized in that: be the single medicinal material that aqueous extract of lignum sappan is used as anti-organ transplantation acute rejection.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 01127907 CN1393250A (en) | 2001-07-04 | 2001-07-04 | Aqueous extract of sapanwood for treating acute rejection reaction after organ transplantation |
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| CN 01127907 CN1393250A (en) | 2001-07-04 | 2001-07-04 | Aqueous extract of sapanwood for treating acute rejection reaction after organ transplantation |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101904892A (en) * | 2010-05-22 | 2010-12-08 | 山西省肿瘤医院 | Preparation process for Sappan Wood extract perfusate and application thereof in treating bladder cancer |
| CN101411739B (en) * | 2008-10-27 | 2011-10-26 | 山西省肿瘤医院 | Method for preparing Caesalpinia sappan water extract |
-
2001
- 2001-07-04 CN CN 01127907 patent/CN1393250A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101411739B (en) * | 2008-10-27 | 2011-10-26 | 山西省肿瘤医院 | Method for preparing Caesalpinia sappan water extract |
| CN101904892A (en) * | 2010-05-22 | 2010-12-08 | 山西省肿瘤医院 | Preparation process for Sappan Wood extract perfusate and application thereof in treating bladder cancer |
| CN101904892B (en) * | 2010-05-22 | 2012-06-06 | 山西省肿瘤医院 | Preparation process for Sappan Wood extract perfusate and application thereof in treating bladder cancer |
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