CN103027910A - Application of indol-3-carbinol in preparation of medicine for treating experimental pulmonary fibrosis - Google Patents
Application of indol-3-carbinol in preparation of medicine for treating experimental pulmonary fibrosis Download PDFInfo
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Abstract
The invention discloses an application of indol-3-carbinol in preparation of a medicine for treating experimental pulmonary fibrosis. Mouse and rat pulmonary fibrosis animal models are copied by intratracheally instilling bleomycin (BLM); indol-3-carbinol is selected as a treating medicine; the influence of indol-3-carbinol on related biochemical indexes and pathological alteration of pulmonary fibrosis animal lung tissue and serum is searched; and the prevention and treating effects on the pulmonary fibrosis animal models by indol-3-carbinol are observed, so that the experimental basis is provided for preventing the pulmonary fibrosis by indol-3-carbinol.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of indole-3-carbinol and prevent and treat application in the experimental pulmonary fibrosis medicine in preparation.
Background technology
Lung (matter) fibrosis (pulmonary fibrosis, PF) be that a kind of agnogenic Diffuse alveolar is scorching and alveolar structure is disorderly, thereby cause alveolar, interstitial pulmonary fibrosis, finally cause the disease of respiratory failure, also being the common final result of the acute and chronic pulmonary disease that causes of many reasons, is a kind of lung occlusive disease of serious harm human health.Inflammation, oxidative stress play an important role in the pulmonary fibrosis pathogenesis.In the clinical research of pulmonary fibrosis, mainly concentrate on idiopathic pulmonary interstitial fibrosis (Idiopathic pulmonary fibrosis, IPF) aspect, this disease is take abnormity damage, fibroblast proliferation and the extracellular matrix remodeling of alveolar epithelial cells as main pathological change, can make the lung tissue afunction, finally cause respiratory failure and cause dead fatefulue interstitial diseases.Pulmonary fibrosis sickness rate in recent years is in rising trend, and morbidity is many, and M-F is 2:1 above middle age, and the mean age is 66 years old, and sickness rate increased with the age, and the mean survival time from diagnosis to death is 3.2 to 5 years.The treatment of PF is main mainly with hormone and immunosuppressant at present, and effect is unsatisfactory.
Indole-3-carbinol (indole-3-carbinol, I3C) is present in Cruciferae class edible vegetable such as Caulis et Folium Brassicae capitatae, Brassica oleracea L.var.capitata L., Caulis et Folium Brassicae capitatae flower etc. in a large number.Clinical experiment and zoopery all confirm, and the I3C toxic and side effects is little, and safety range is wider.The research discovery, I3C has inhibition tumor cell propagation and cell death inducing, removing oxygen-derived free radicals and lipoid peroxidization resistant.The research report is arranged, and I3C can treat the rat liver fibrosis due to the complex factors effectively, and its mechanism is active with its enhancing MMPs, promote the ECM degraded, and antioxidation is relevant.I3C causes the impact of pulmonary fibrosis on bleomycin, so far there are no reports.
Summary of the invention
The object of the invention is to provide a kind of indole-3-carbinol to cause application in the Mouse and rat pulmonary fibrosis medicine at preparation control bleomycin.
In order to solve the problems of the prior art, technical scheme provided by the invention is as follows:
The application of a kind of indole-3-carbinol in the medicine of preparation prevention or treatment pulmonary fibrosis.
Preferably, described pulmonary fibrosis is experimental pulmonary fibrosis.
Preferably, described experimental pulmonary fibrosis is mice or the Pulmonary Fibrosis in Rats animal model due to the bleomycin.
Preferably, described medicine contains the pharmaceutically indole-3-carbinol of effective dose, with the upper acceptable carrier of pharmacology.
Copy Mouse and rat pulmonary fibrosis animal model by intratracheal instillation bleomycin (Bleomycin, BLM) in the technical scheme of the present invention.The present invention selects indole-3-carbinol as medicine first, the research indole-3-carbinol is to pulmonary fibrosis animal lung tissue and serum related biochemical indicator and pathological change, observe indole-3-carbinol to the preventive and therapeutic action of pulmonary fibrosis animal model, provide experimental basis thereby treat pulmonary fibrosis for indole-3-carbinol.
Indole-3-carbinol (Indole-3-carbinol, I3C) in the technical solution of the present invention, its another name: 3-Indolemethanol, the 3-indole-alcohol, structural formula is
Molecular formula (Xi Er representation) is C
9H
9NO, molecular weight: 147.17.
The inventor finds under study for action, indole-3-carbinol causes pulmonary fibrosis mice and rats gavaged after 28 days to bleomycin, the administration group is little, in, heavy dose of group Mouse and rat alveolitis and pulmonary fibrosis degree alleviate or obviously alleviate (P＜0.05, P＜0.01) (embodiment one); Pulmonary fibrosis mice and rat body weight are obviously increased, and the lung coefficient obviously reduces (P＜0.05, P＜0.01) (embodiment two); Hydroxyproline (HYP) content that can indirectly reflect collagen content in lung tissue and the serum reduces (P＜0.05, P＜0.01) (embodiment three); Indole-3-carbinol can strengthen the Total antioxidant capacity (T-AOC) of pulmonary fibrosis mice serum, You Yida, middle dosage group be (P＜0.01) obviously, can strengthen the Total antioxidant capacity (T-AOC) of lung fibrosis in rats tissue and serum, (P＜0.05, P＜0.01) (embodiment four) above-mentioned experimental result shows, indole-3-carbinol has the effect of remarkable pulmonary fibrosis resistant, and this mechanism of action is synthetic relevant with deposition and fibroblast proliferation etc. with antiinflammatory antioxidation, the inhibition intercellular substance collagen of indole-3-carbinol.Given this, the drug candidate for the treatment of pulmonary fibrosis be might become by indole-3-carbinol of the present invention, prevention and the treatment of lung occlusive disease, particularly pulmonary fibrosis are used for.Therefore, the purpose of this invention is to provide indole-3-carbinol and prevent and/or treat the lung occlusive disease, particularly the application in the medicine of pulmonary fibrosis disease.
With respect to scheme of the prior art, the present invention has following characteristics and advantage:
1. indole-3-carbinol can obviously alleviate the inflammatory reaction of pulmonary fibrosis mice and rat pulmonary, alleviates the pulmonary fibrosis degree.
2. indole-3-carbinol can significantly increase the body weight of pulmonary fibrosis mice and rat, the lung coefficient of reduction Mouse and rat pulmonary fibrosis model.
Indole-3-carbinol can obviously reduce in pulmonary fibrosis mice and the lung tissue of rats and serum in hydroxyproline (HYP) content, improve total antioxidation (T-AOC) ability in the pulmonary fibrosis mice serum, improve total antioxidation (T-AOC) ability in lung fibrosis in rats tissue and the serum.
Description of drawings
The invention will be further described below in conjunction with drawings and Examples:
Fig. 1 is indole-3-carbinol causes Mouse and rat pulmonary fibrosis impact on bleomycin pathological observation result (E * 100); Wherein Fig. 1-A is the Normal group mice, and lung tissue structure is clear, and alveolar wall is complete, and alveolar septum has no and thickens and cell infiltration.Fig. 1-B is the model group mice, and alveolar structure is disorderly, and alveolitis is obvious, and alveolar septum fibroblast and substrate deposit in a large number, present typical pulmonary fibrosis pathological changes.
Fig. 1-C is the heavy dose of group of indole-3-carbinol mice, and lung tissue structure is clear, and alveolar wall is still complete, the slight hypertrophy of alveolar septum fibroblast, and a small amount of inflammatory cell infiltration, collagen deposition significantly reduces.Fig. 1-D is dosage group mice in the indole-3-carbinol, lung tissue structure's light damage, and the subregion alveolar septum slightly thickens, the slight hypertrophy of fibroblast, a small amount of inflammatory cell infiltration, the collagen deposition amount reduces.Fig. 1-E is indole-3-carbinol small dose group mice, and the part alveolar structure destroys, and alveolar wall slightly thickens, and the mild fibrosis focus is arranged, the affected area inflammatory cell infiltration.The positive contrast medicated vinegar acid of Fig. 1-F prednisone group mice, the part alveolar structure destroys, the slight broadening of alveolar septum, fibroblast proliferation and collagen fiber deposition degree alleviate.
Fig. 2 is indole-3-carbinol causes the impact of lung fibrosis in rats lung tissue on bleomycin pathology and observed result (E * 100); Wherein Fig. 2-A is rats in normal control group, and lung tissue structure is clear, and alveolar wall is complete, and alveolar septum has no and thickens, and alveolar space is bright, and intracavity has no inflammatory exudation.Fig. 2-B is the model group rat, and lung tissue structure is disorderly, and alveolar septum significantly thickens, and alveolar space narrows down or disappears, a large amount of hypertrophy of fibroblast, and inflammatory cell infiltration, the collagen fiber deposition, interstitial pulmonary fibrosis forms.
Fig. 2-C is the heavy dose of group of indole-3-carbinol rat, and slight pathological change, alveolar structure are slightly disorderly, the slight hypertrophy of alveolar septum fibroblast, and a small amount of inflammatory cell infiltration, collagen deposition significantly reduces.Fig. 2-D is dosage group rat in the indole-3-carbinol, lung tissue structure's light damage, and the subregion alveolar septum slightly thickens, and inflammatory cell infiltrates on a small quantity, and the collagen deposition amount reduces.Fig. 2-E is indole-3-carbinol small dose group rat, and the part alveolar structure destroys, and alveolar septum has the mild fibrosis focus because of cell infiltration and fibroblast proliferation broadening, the affected area inflammatory cell infiltration.The positive contrast medicated vinegar acid of Fig. 2-F prednisone group rat, alveolar septum broadening obviously alleviates than model group, and fibroblast and collagen deposition reduce.
Fig. 3 is that indole-3-carbinol causes lung fibrosis in rats lung tissue Masson dyeing pathological observation (E * 100) to bleomycin; Wherein Fig. 3-A be rats in normal control group without obvious pathological change, alveolar structure is clear, alveolar is bright, alveolar septum is normal.Fig. 3-B is the model group rat, and lung tissue structure is disorderly, the remarkable broadening of alveolar septum, and the amount of collagen fiber significantly increases, extrtacellular matrix deposition, alveolar fracture, fusion, structural deterioration are obvious.
Fig. 3-C is the heavy dose of group of indole-3-carbinol rat, and lung tissue structure is clear, and alveolar wall is still complete, the slight hypertrophy of alveolar septum fibroblast, and collagen deposition significantly reduces, and the pulmonary fibrosis degree obviously alleviates.Fig. 3-D is dosage group rat in the indole-3-carbinol, lung tissue structure's light damage, and the subregion alveolar septum slightly thickens, and fibroblast and collagen deposition amount reduce.Fig. 3-E is indole-3-carbinol small dose group rat, and alveolar structure is disorderly, and alveolar wall slightly thickens, and the mild fibrosis focus is arranged.The positive contrast medicated vinegar acid of Fig. 3-F prednisone group rat, alveolar septum is broadening slightly, the slight hypertrophy of fibroblast, collagen fiber deposition degree obviously alleviates.
The specific embodiment
Below in conjunction with specific embodiment such scheme is described further.Should be understood that these embodiment are not limited to limit the scope of the invention for explanation the present invention.The implementation condition that adopts among the embodiment can be done further adjustment according to the condition of concrete producer, and not marked implementation condition is generally the condition in the normal experiment.
One, material
1. laboratory animal
The SD rat, male, body weight 200 ± 20 grams, the cleaning level is provided credit number: scxk(Shanghai) 2009-005. by Shanghai Slac Experimental Animal Co., Ltd..Experimental animal feeding is in cleaning level animal observation ward, and adaptability was fed 3 days, the feed of freely drinking water during the administration.
2. medicine and reagent
Indole-3-carbinol (Indole-3-carbinol, I3C, another name: 3-Indolemethanol, structural formula:
), molecular formula (Xi Er representation) C9H9NO, molecular weight: 147.17, white powder, Sigma company; U.S.'s bleomycin, Nippon Kayaku K. K, lot number:, 640110; Prednisone acetate tablets, white plates, specification: the 5mg/ sheet, packing: 100 slices/bottle, product batch number: 100318, the accurate word H32022681 of traditional Chinese medicines, Xuzhou zero diopter Pharmaceutical Co, production lot number: 080140; Benzylpenicillin sodium for injection, specification: 800,000 units, batch number: Y1010105, the accurate word H13020657 of traditional Chinese medicines, Huabei Pharmaceutic Co., Ltd.Total antioxidant capacity (T-AOC) detection kit, hydroxyproline (HYP) detection kit, bio-engineering corporation is built up in Nanjing.
3. instrument
Electronic balance: the EL104 type, the more flat scientific instrument company limited in Shanghai is produced; Table model high speed centrifuge: the H1650 type, instrument experimental apparatus development corporation, Ltd. in Hunan, Hunan produces; The electric heating constant temperature tank: the HH-S26S type, Jintan City the earth self-reacting device factory produces; Ultraviolet-uisible spectrophotometer: T6 new century, Beijing Puxi General Instrument Co., Ltd; High speed disperser (interior cut refiner): XHF-D, NingBo XinZhi Biology Science Co., Ltd; Inverted fluorescence microscope: X71 type, Olympus company, Japan; Table model high speed centrifuge: H-1650, Hunan, Hunan instrument Laboratory Instruments development corporation, Ltd.; High speed low temperature centrifugal machine: 5417R type, Eppendorf company, Germany.
Two, method
1. modeling and administration
48 of experimental mouse, male, weigh, numbering, be divided at random 6 groups by body weight, namely Normal group, model group, indole-3-carbinol large (100mg/kg), in (50mg/kg) and little (25mg/kg) dosage group and positive control drug prednisolone acetate group, 8 every group.Model group and each treatment group adopt BLM to copy the animal pulmonary fibrosis model.Concrete operation step is as follows: during experiment, animal is with 4% chloral hydrate (0.01ml/g) intraperitoneal injection of anesthesia, the operating-table of lying on the back, fixing head and extremity, routine disinfection, the descending neck median incision of aseptic condition, blunt separation exposes trachea, the 1ml syringe thrusts model group, each treatment group of indole-3-carbinol and prednisolone acetate group Mouse and rat tracheal cartilages czermak space and slowly injects BLM A5(5mg/kg), Normal group injects the equal-volume normal saline under the same conditions.Immediately that animal is upright after the injection, along long axis of body left rotation and right rotation 3-5min, medicinal liquid is uniformly distributed in the lung of both sides, then skin suture, sterilization send cleaning level observation ward conventional the raising after animal is clear-headed.Whole operation process is strictly followed sterile working's principle.Front 1 day of art and postoperative continuous intramuscular injection 800,000 unit penicillin sodiums of all animals (0.5ml/ only) on the 3rd.Each treated animal begins according to corresponding body weight gastric infusion in the modeling second day, and normal group and model group give equal-volume 5% sodium carboxymethyl cellulose (CMC Na), every other day weighs once successive administration 28 days.
2. collection of specimens
Each is organized laboratory animal and puts to death fasting in front 12 hours, can't help water, processes and weighs the same day, gets blood execution after the anesthesia and respectively organizes laboratory animal.Open breast under the aseptic condition and isolate trachea and both sides lungs, weigh.The right lung inferior lobe places 4% paraformaldehyde fixing, routine paraffin wax embedded section, HE dyeing; Get middle lobe of right lung 30 ~ 100mg and place 10ml glass centrifuge tube with scale ,-80 ℃ of Refrigerator stores are in order to measuring the content of hydroxyproline in each experimental mice lung tissue;
The preparation of lung tissue homogenate: lung tissue is weighed, and adds the ice normal saline of 9 times of lung tissue weight, and interior cut Potter-Elvehjem Tissue Grinders is made 10% lung tissue homogenate, and-80 ℃ of Refrigerator stores are to survey tissue T-AOC.
The preparation of serum: each treated animal is got the centrifugal 10min of 3500r/min behind the blood, carefully gets supernatant and places in the 1.5ml centrifuge tube, and the supernatant after the transfer is the centrifugal 10min of 3500r/min again.The serum solution for preparing-80 ℃ Refrigerator store is to measure HYP and T-AOC biochemical indicator in the serum.
3. lung coefficient
Calculate as follows the lung coefficient, heavy (the mg)/body weight (g) of lung coefficient=lung.Because pulmonary fibrosis Earlier period of inflammation cell oozes out in a large number, a large amount of hypertrophy of fibroblast in late period, collagen over-deposit all can cause the lung coefficient to increase, so but lung coefficient this index indirect reaction pulmonary fibrosis Mus inflammation and Fibrotic degree.
4. pathological study
The bottom right lung tissue is fixed with 4% formalin, and through dehydration of alcohol step by step, dimethylbenzene is transparent, waxdip, paraffin embedding, conventional section 4 μ m, rear row HE, Masson dyeing.Determine the alveolitis of lung tissue and the degree of pulmonary fibrosis with reference to Szapiel method optical microphotograph Microscopic observation.This lesion degree is divided into level Four: 0 grade of nothing obviously changes; 1 grade of MC, extent of disease is less than 20% of full lung; 2 grades of moderates change, and extent of disease accounts for the 20%-50% of full lung; 3 grades of severes change, and extent of disease accounts for more than 50% of full lung.Adopt the method for Ashcroft and H ü bner, adopt single blind method 8 visuals field of casual inspection from every group of pulmonary fibrosis sample to observe the pulmonary fibrosis degree: 0 grade, normal lung; 1 grade, the slight swelling of alveolar, local slight fiber occurs; 2 grades, significantly (alveolar wall is greater than normal 3 times) appear in fibrosis, the fiber kitchen range occurs; 3 grades, continuous zone of fiber (alveolar wall is greater than normal 3 times); 4 grades, the fiber kitchen range appears, and area is less than 10%; 5 grades, the fiber kitchen range merges, fiber area 10%～50%, and alveolar structure destroys significantly; 6 grades, large stretch of continuous fiber kitchen range (greater than 50%); 7 grades, alveolar space is full of fibrous tissue, bulla occurs; 8 grades, complete fibrosis; Counted 1 minute for 1 grade, every group of 8 samples are marked respectively, and average.
5. lung tissue and serum Biochemical Indexes are measured
The 0.5ml hydrolyzed solution is accurately added in the scale teat glass of freezing preservation fritter lung tissue, and mixing is added a cover rear boiling water bath hydrolysis 20 minutes, and 10 minutes mixings once therebetween.In vitro the liquid pH value transfers to about 6.5 afterwards, adds proper amount of active carbon, mixing, be transferred in the 1.5ml centrifuge tube, the centrifugal 10min of 3500r/min gets supernatant 0.5ml, adds successively reagent one, reagent two, reagent three, mixing, 60 ℃ of water-bath 15min, the centrifugal 10min of 3500r/min after the cooling gets supernatant in microspectrophotometer 550nm, measure the absorbance of each pipe under the 1cm optical path, the by specification formula calculates HYP content in the lung tissue.Serum HYP and T-AOC, tissue T-AOC operates in strict accordance with the test kit description.
6. statistical method
Adopt SPSS 12.0 statistical software processing systems, experimental data with
Expression, measurement data is checked with t; The class count data is carried out the t check after being converted into measurement data, diversity between comparable group, and there is statistical significance P＜0.05.
Three, result of implementation
(1) indole-3-carbinol is on the impact of experimental pulmonary fibrosis mice
(1) indole-3-carbinol causes the impact of pulmonary fibrosis mice lung morphology on bleomycin
The experiment mice lung tissue is through the parallel HE dyeing of paraffin section, and observed result shows under the light microscopic: normal group mouse lung organizational structure is clear, and alveolar space is bright, and alveolar wall is complete, and alveolar septum has no and thicken, has no cell infiltration.Model group mouse lung organizational structure is disorderly, and alveolar space narrows down or disappears, and alveolar septum significantly thickens, a large amount of fibroblast proliferations of interstitial lung and collagen fiber deposition, and the prompting interstitial pulmonary fibrosis forms.Compare the heavy dose of group of indole-3-carbinol mouse lung with model group mouse lung tissue and organize alveolar inflammation and pulmonary fibrosis degree significantly to alleviate (P＜0.01), dosage group mouse lung organizes alveolitis and pulmonary fibrosis lesion degree significantly to alleviate (P＜0.01) in the indole-3-carbinol; Indole-3-carbinol small dose group mouse lung organizes alveolitis and pulmonary fibrosis lesion degree to alleviate (P＜0.05); Prednisolone acetate group mouse lung organizes alveolitis and pulmonary fibrosis degree significantly to alleviate (P＜0.01).See Table 1, Fig. 1.
Table 1 Effect of I3C on alveolitis and fibrosis extent of pulmonary fibrosis mouse
##p＜0.01vs?control?group；*p＜0.05,**p＜0.01?vs?model?group
(2) indole-3-carbinol causes the impact of pulmonary fibrosis mice body weight and lung coefficient on bleomycin
Behind the animal model, model group Mouse Weight compared with normal group significantly reduces (P＜0.01), comparing the big or middle dosage group of indole-3-carbinol Mouse Weight with model group significantly increases (P＜0.01), and indole-3-carbinol small dose group, prednisone group mice are compared body weight with model group increase (P＜0.05); Model group mouse lung coefficient is significantly higher than Normal group mice (P＜0.01); Compare with model group mouse lung coefficient, the lung coefficient of the former big or middle dosage group mice of indole-3-all significantly reduces (P＜0.01), and the lung coefficient of indole-3-carbinol small dose group, prednisone group mice reduces (P＜0.05).See Table 2.
Table 2 Effects of I3C on body weight, pulmonary index of pulmonary mouse (
N=8)
##p＜0.01vs?control?group；*p＜0.05,**p＜0.01?vs?model?group
(3) indole-3-carbinol causes the impact of pulmonary fibrosis mice lung tissue and serum HYP content on bleomycin
Compare with the normal group mice, model group mouse lung tissue and Serum oxyproline (HYP) content significantly increases (P＜0.01).Compare with model group mice serum HYP content, the big or middle dosage group of indole-3-carbinol, prednisolone acetate group mice serum HYP content significantly reduces (P＜0.05), and indole-3-carbinol small dose group mouse lung tissue and serum HYP content reduce (P＜0.05), see Table 3.
Table 3 Effect of I3C on levels of HYP of pulmonary fibrosis mouse in the lung tissue andserum(
N=8)
##p＜0.01vs?control?group；*p＜0.05,**p＜0.01?vs?model?group
(4) indole-3-carbinol causes the impact of pulmonary fibrosis mice serum T-AOC amount on bleomycin
Compare with normal group, model group mice serum Total antioxidant capacity (T-AOC) significantly reduces (P＜0.01); Compare with model group, the big or middle dosage group of indole-3-carbinol mice serum T-AOC significantly increases (P＜0.01), prednisolone acetate group mice serum T-AOC increases (P＜0.05), and increase trend is arranged indole-3-carbinol mice serum T-AOC but not statistically significant (P＞0.05); See Table 4.
Table 4 Effect of I3C on levels of T-AOC in serum of pulmonary fibrosis mouse(
N=8)
##p＜0.01vs?control?group；*p＜0.05,**p＜0.01?vs?model?group
(2) indole-3-carbinol causes the impact of lung fibrosis in rats on bleomycin
(1) indole-3-carbinol causes the impact of lung fibrosis in rats lung morphology on bleomycin
The experimental rat lung tissue is through the parallel HE of paraffin section and Masson dyeing, and observed result shows under the light microscopic: normal rats lung tissue structure is clear, and alveolar space is bright, and alveolar wall is complete, and alveolar septum has no and thicken, has no cell infiltration.Model group lung tissue structure is disorderly, and alveolar space narrows down or disappears, and alveolar septum significantly thickens, a large amount of fibroblast proliferations of interstitial lung and collagen fiber deposition, and the prompting interstitial pulmonary fibrosis forms.Compare indole-3-carbinol heavy dose of group lung tissue of rats alveolitis and pulmonary fibrosis degree with the model group lung tissue of rats and significantly alleviate (P＜0.01), dosage group lung tissue of rats alveolitis and pulmonary fibrosis lesion degree significantly alleviate (P＜0.01) in the indole-3-carbinol; Indole-3-carbinol small dose group lung tissue of rats alveolitis and pulmonary fibrosis lesion degree alleviate (P＜0.05, P＜0.01); Compare prednisolone acetate group lung tissue of rats alveolitis and pulmonary fibrosis degree with the model group rat and significantly alleviate (P＜0.01).See Table 5, Fig. 2, Fig. 3.
Table 5 Effect of I3C on alveolitis and fibrosis extent of pulmonary fibrosis mouse(
N=8)
##p＜0.01vs?control?group；*p＜0.05,**p＜0.01?vs?model?group
(2) indole-3-carbinol causes the impact of lung fibrosis in rats body weight and lung coefficient on bleomycin
Behind the animal model, model group rat body weight compared with normal group significantly reduces (P＜0.01), and comparing each dosage group rat body weight of indole-3-carbinol with model group significantly increases (P＜0.01), and prednisone group rat body weight increases (P＜0.05); Model group induced lung coefficient is significantly higher than rats in normal control group (P＜0.01); Compare with model group induced lung coefficient, the lung coefficient of the former big or middle dosage group rat of indole-3-all significantly reduces (P＜0.01), and the lung coefficient of indole-3-carbinol small dose group, prednisone group rat reduces (P＜0.05).See Table 6.
Table 6 Effects of I3C on body weight, pulmonary index ofpulmonary rats (
N=8)
##p＜0.01vs?control?group；*p＜0.05,**p＜0.01?vs?model?group
(3) indole-3-carbinol causes the impact of lung fibrosis in rats lung tissue and serum HYP content on bleomycin
Compare with normal rats, model group lung tissue of rats and Serum oxyproline (HYP) content significantly increases (P＜0.01).Compare with model group rat HYP content, the big or middle dosage group of indole-3-carbinol, prednisolone acetate group lung tissue of rats and serum HYP content significantly reduce (P＜0.01), indole-3-carbinol small dose group lung tissue of rats HYP content significantly reduces (P＜0.01), and serum HYP content reduces (P＜0.05) and sees Table 7.
Table 7 Effect of I3C on levels of HYP of pulmonary fibrosis rats in the lung tissue andserum (
N=8)
##p＜0.01vs?control?group；*p＜0.05,**p＜0.01?vs?model?group
(4) indole-3-carbinol causes the impact of lung fibrosis in rats serum T-AOC amount on bleomycin
Compare with normal group, model group lung tissue of rats and serum Total antioxidant capacity (T-AOC) significantly reduce (P＜0.01); Compare with model group, the big or middle dosage group of indole-3-carbinol and the prednisone group T-AOC of rat tissue significantly increase (P＜0.01), and indole-3-carbinol small dose group tissue T-AOC increases (P＜0.05); Compare with model group, the heavy dose of group of indole-3-carbinol serum T-AOC significantly increases (P＜0.01), in the indole-3-carbinol, small dose group and prednisone group serum T-AOC increase and see that (P＜0.05) sees Table 8.
Table 8 Effect of I3C on levels of T-AOC of pulmonary fibrosis rats in the lung tissue and serum(
N=8)
##p＜0.01vs?control?group；*p＜0.05,**p＜0.01?vs?model?group
In sum, according to result of implementation as can be known:
1. the histopathology observed result shows, the experimental pulmonary fibrosis Mouse and rat gave the indole-3-carbinol treatment after 28 days, and alveolitis and the fibrosis of lung tissue obviously alleviate.
2. successive administration is after 28 days, and indole-3-carbinol can increase the body weight of pulmonary fibrosis mice and rat, reduces significantly the lung coefficient.And the alveolitis of lung tissue and lung fiber degree are significantly alleviated.The above results shows, indole-3-carbinol has the effect of certain control pulmonary fibrosis.
3. give the experimental animal indole-3-carbinol and gavage treatment after 28 days, pulmonary fibrosis mice and lung tissue of rats and intraserous hydroxyproline (HYP) content obviously reduce, point out its anti-fibrosis effect may with suppress lung tissue in the generation of collagen relevant.
4. after giving indole-3-carbinol and gavaging 28 days, Total antioxidant capacity (T-AOC) obviously strengthens in the mice serum, and Total antioxidant capacity (T-AOC) obviously strengthens in lung tissue of rats and the serum.The above results demonstration, indole-3-carbinol also may realize that it is to the preventive and therapeutic effect of pulmonary fibrosis by antioxidation.
In sum, indole-3-carbinol causes experimental pulmonary fibrosis to bleomycin and has certain preventive and therapeutic effect, and this effect is relevant with antiinflammatory oxidation resistance, the interior collagenation of inhibition lung tissue of its increase body.
The present invention is described in conjunction with example, yet after having read foregoing of the present invention, those skilled in the art can understand and do many changes in disclosed embodiment and also can obtain same or similar result, and do not exceed design of the present invention, spirit and scope.More particularly, obviously some chemistry and alternative reagent disclosed herein of physiological related reagent and obtain same or similar result.All similarly replace and modify for a person skilled in the art, obviously think all that namely all above-mentioned these equivalent form of values all fall within the application's appended claims limited range equally in spirit of the present invention, scope and design and the claim scope.
Claims (4)
1. the application of indole-3-carbinol in the medicine of preparation prevention or treatment pulmonary fibrosis.
2. the application of indole-3-carbinol according to claim 1 in the medicine of preparation prevention or treatment pulmonary fibrosis is characterized in that described pulmonary fibrosis is experimental pulmonary fibrosis.
3. the application of indole-3-carbinol according to claim 2 in the medicine of preparation prevention or treatment pulmonary fibrosis is characterized in that described experimental pulmonary fibrosis is mice or the Pulmonary Fibrosis in Rats animal model due to the bleomycin.
4. the application of indole-3-carbinol according to claim 2 in the medicine of preparation prevention or treatment pulmonary fibrosis is characterized in that described medicine contains the pharmaceutically indole-3-carbinol of effective dose, with the upper acceptable carrier of pharmacology.
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|---|---|---|---|---|
| CN116270822A (en) * | 2023-04-21 | 2023-06-23 | 莱檬(清远市)生物科技有限公司 | Plant extract for relieving pulmonary fibrosis as well as preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2007005879A2 (en) * | 2005-07-01 | 2007-01-11 | The Johns Hopkins University | Compositions and methods for the treatment or prevention of disorders relating to oxidative stress |
| WO2010059245A2 (en) * | 2008-11-21 | 2010-05-27 | The Johns Hopkins University | Compositions and methods for treating or preventing radiation injury |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007005879A2 (en) * | 2005-07-01 | 2007-01-11 | The Johns Hopkins University | Compositions and methods for the treatment or prevention of disorders relating to oxidative stress |
| WO2010059245A2 (en) * | 2008-11-21 | 2010-05-27 | The Johns Hopkins University | Compositions and methods for treating or preventing radiation injury |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116270822A (en) * | 2023-04-21 | 2023-06-23 | 莱檬(清远市)生物科技有限公司 | Plant extract for relieving pulmonary fibrosis as well as preparation method and application thereof |
| CN116270822B (en) * | 2023-04-21 | 2024-03-15 | 广东冠清柠生物科技有限公司 | Plant extract for relieving pulmonary fibrosis as well as preparation method and application thereof |
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