CN102397291A - Use of lithium chloride in preparation of drug for inhibiting keratinocyte over proliferation diseases - Google Patents
Use of lithium chloride in preparation of drug for inhibiting keratinocyte over proliferation diseases Download PDFInfo
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- CN102397291A CN102397291A CN2011102422076A CN201110242207A CN102397291A CN 102397291 A CN102397291 A CN 102397291A CN 2011102422076 A CN2011102422076 A CN 2011102422076A CN 201110242207 A CN201110242207 A CN 201110242207A CN 102397291 A CN102397291 A CN 102397291A
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Abstract
The invention relates to a use of lithium chloride in preparation of a drug for inhibiting keratinocyte over proliferation diseases. The keratinocyte over proliferation diseases comprise psoriasis, ichthyosis and keratinocyte tumors. The use of lithium chloride in preparation of a drug for inhibiting keratinocyte over proliferation diseases is a novel use of lithium chloride in pharmacy and develops a novel application field. Lithium chloride has good treatment effects on skin diseases such as psoriasis, ichthyosis and keratinocyte tumors which are caused by keratinocyte over proliferation or are characterized by keratinocyte over proliferation. Through existing utilization of lithium chloride in other clinical drugs, it is shown that lithium chloride has very small toxic and side effects and is safe for use.
Description
Technical field
The present invention relates to the new purposes of lithium chloride in pharmaceutical field, specifically, relate to lithium chloride and suppress the application in the keratinocyte hyperplasia medicine in preparation.
Background technology
Lithium chloride (LiCL), inorganic compound, chemical formula is: LiCL, molecular weight 42.4 is white cube crystalline powder, in air, is prone to deliquescence, water-soluble, ethanol and acetone etc., it is neutral or acid that aqueous solution is.This chemical compound is a kind of antipsychotic drug commonly used, is usually used in treating bipolar affective disorder.Also there is bibliographical information to claim that lithium chloride can suppress the propagation of various kinds of cell, comprises many tumor cells, osteosarcoma cell for example, HCC, prostate gland cancer cell.
The skin of human body is made up of epidermis, corium and subcutaneous tissue three parts.Keratinocyte is a kind of keratoprotein cell of epidermis, is the important component part that constitutes epidermis.Under the normal condition, the human epidermal cell is bred regularly, is broken up and comes off, and is keeping the balance that skin sugar, protein, fat, power and water are separated matter, has functions such as protection self, regulate body temperature, drainage refuse and immunomodulating.Normal person's skin looks nature, level and smooth, moist, glossy and high resilience.But when the keratinocyte proliferative disorder, then can cause some diseases.Common clinically various skin disease is like psoriasis, ichthyosis and keratinocyte tumor etc., all relevant with the hyper-proliferative of keratinocyte at present.One of dermopathic principal character of this type is that the keratinization degree is high.Psoriasis for example, this disease are that a kind of common recurrent inflammatory skin is sick, are commonly called as psoriasis; Skin lesion be general of symmetry on cover maculopapule, the speckle of silvery white squama, compare psoriatic keratinocyte propagation, differentiation, adjusting and Developmental and Metabolic Disorder with normal person's keratinocyte; The epidermis cell hyper-proliferative; The renewal of nuclear of epidermal cells split speed and epidermis cell is obviously accelerated than the normal person, shows as epidermis and thickens and tangible silvery white squama is arranged, thereby cause many-sided dysfunction such as immunity, secretion of skin; And pathogenesis that should disease is very complicated, does not illustrate fully as yet so far.This type skin disorder also shows the characteristics that are difficult to thoroughly radical cure and are prone to recurrence, is having a strong impact on patient's live and work, and their physical and mental health is caused serious injury especially.Therefore, need a kind of keratinocyte that suppresses badly and breed, and then reduce the medicine that squama produces, to alleviate or radical cure psoriasis, ichthyosis and keratinocyte tumor.But also do not appear in the newspapers about the purposes of lithium chloride in suppressing keratinocyte propagation at present.
Summary of the invention
The objective of the invention is provides the new purposes of a kind of lithium chloride in pharmacy to deficiency of the prior art.
For realizing above-mentioned purpose, the technical scheme that the present invention takes is:
Lithium chloride suppresses the application in the keratinocyte hyperproliferation disease medicine in preparation.
Said cell hyperproliferation disease is a psoriasis;
Said cell hyperproliferation disease is an ichthyosis;
Said cell hyperproliferation disease is the keratinocyte tumor.
The invention has the advantages that:
1, excavates the new purposes of lithium chloride in pharmacy, opened up a new application.
2, lithium chloride can significantly suppress keratinocyte propagation; To what cause by the keratinocyte hyper-proliferative; Or be the skin disorder of characteristic with the keratinocyte hyper-proliferative, like psoriasis, ichthyosis and keratinocyte tumor, have excellent curative.
3, lithium chloride uses in clinical other drug, proves that its toxic and side effects is minimum, and therefore, for being applied in treatment keratinocyte hyperproliferation disease, treatment psoriasis, ichthyosis and keratinocyte tumor aspect can relievedly be used.
Description of drawings
Accompanying drawing 1 is the influence of lithium chloride to mice keratinocyte propagation.
Accompanying drawing 2 is mice keratinocyte BrDU colored graphs that lithium chloride is handled.
Accompanying drawing 3A is that lithium chloride induces keratinocyte that the analysis chart A that the S phase blocks takes place.
Accompanying drawing 3B is that lithium chloride induces keratinocyte that the analysis chart B that the S phase blocks takes place.
Accompanying drawing 3C is that lithium chloride induces keratinocyte that the analysis chart C that the S phase blocks takes place.
Accompanying drawing 3D is that lithium chloride induces keratinocyte that the analysis chart D that the S phase blocks takes place.
Accompanying drawing 4 is lithium chloride influences to albumen β-catenin and PCNA expression.
The specific embodiment
Below in conjunction with the specific embodiment the present invention is described further.
Embodiment 1
Lithium chloride suppresses the keratinocyte proliferation test
This tests used lithium chloride available from U.S. Sigma company.Use aseptic 1 * phosphate buffer PBS to be formulated as 4M concentration, nylon mesh is filtered, and-4 ℃ of preservations are subsequent use; MTS/PMS liquid is available from U.S. Promega company; Reagent such as β-catenin, c-myc, cyclinD1, p53, p21, PCNA are purchased respectively in U.S. Cell Signaling Technology company and Santa Cruz company.Used mice keratinocyte is to make through former generation keratinocyte of cultivating american cancer research association.
1, the MTS/PMS method detects lithium chloride forms cell proliferation to cutin influence
Use the MTS/PMS method to detect lithium chloride forms cell proliferation to cutin influence; The result shows: adopt from 0.5mM to 40mM variable concentrations lithium chloride; Intervene respectively and handle mice keratinocyte 24h; 48h and 72h, lithium chloride begin significantly to suppress keratinocyte growth (see figure 1) greater than 5mM concentration the time.Lithium chloride is at 24h, 48h, and the mice keratinocyte half-inhibition concentration IC50 in the time of 72h is respectively 25.85 ± 5.03, and 16.16 ± 0.95,12.35 ± 1.38mM.
2,5-bromodeoxyuridine nucleoside (BrDU) staining is measured lithium chloride forms cell proliferation to cutin influence
The painted principle of BrDU is: the BrdU of hatching together at cell cycle S phase and cell can infiltrate in the dna molecular, combines BrdU antibody to combine with the BrdU specificity that infiltrates DNA again, just can detect the cell that dna replication dna enlivens.Therefore, utilize BrDU in special time, to mix the state that how much just can reflect cell proliferation of cell.We adopt BrDU fusion method further to observe lithium chloride forms cell proliferation to cutin influence.The result is shown in Fig. 2 A: normal blank group cell growth is normal, and the BrDU positive rate is 71.81 ± 6.79% at matched group, and prompting hyperplasia is active, is in the proliferation index phase.Find that lithium chloride significantly suppresses cell proliferation after adopting lithium chloride to cultivate the intervention cell, along with the increase of lithium chloride concentration; BrDU cell positive rate cell is at 10mM; 20mM, 40mM is respectively 57.91 ± 6.57%, 23.48 ± 3.19% and 9.67 ± 2.45% (seeing Fig. 2 A) after handling 24h.Appear with lithium chloride intervention concentration and breed reduction trend (seeing Fig. 2 B).Simultaneously, Western blot detects the increase that shows along with lithium chloride concentration, and β-catenin protein expression also strengthens (seeing Fig. 2 C) gradually, thereby brings into play significant depression effect.
3, lithium chloride suppresses the mechanism research of keratinocyte propagation
3.1 lithium chloride induces the keratinocyte generation S phase to block
For further understanding lithium chloride to the cutin influence in formation cell cycle, we adopt flow cytometer to detect the distribution situation of cell cycle.Shown in Fig. 3 A to Fig. 3 D: the lithium chloride with variable concentrations is handled 24h, 48h, and 72h, cell cycle take place obviously to change.Particularly at 72h, increase with dosage, S phase and M phase cell showed increased are main with the M phase especially, and G1 phase cell significantly reduces, and can know in conjunction with aforementioned MTS/PMS testing result, and the retardance of S phase and M phase has taken place cell.
3.2 lithium chloride is to the influence of β-catenin and TGF signal beta pathway associated protein
As shown in Figure 4: the lithium chloride intervention is handled and can be caused that β-catenin protein expression raises, and level-off and concentration have certain dependency on it.Meanwhile, along with the increase of concentration, cell proliferation index PCNA protein level also significantly reduces, and in conjunction with the MTS/PMS testing result of front, the prompting cell proliferation is suppressed.
In sum, lithium chloride can significantly suppress the propagation of keratinocyte, and its mechanism of action blocks, activates TGF β apoptotic signal path with the inducing cell S phase relevant.
Embodiment 2
Take by weighing 1.272g lithium chloride powder (available from U.S. Sigma company), add the 1000ml sterilized water, stir, fully dissolve mixing after, divide to install in the aseptic medicine bottle to seal, product is processed in sterilization, shady and cool dry place preserves.
Clinical trial 1: be directed against for 45 routine sick ages more than 2 years, the psoriatic that the state of an illness is similar establishes the treatment group: 15 examples, the lithium chloride solution of obliterating present embodiment; Matched group: 15 examples, obliterating Stigma Croci sativi are revealed (purchase in the Stigma Croci sativi road and hide secret); Blank control group: 15 examples, obliterating normal saline.Three groups Therapeutic Method is: dip in disinfecting cotton swab and get smear, directly be coated onto the psoriatic lesion place, each once 30 days course of treatment, uses 6 courses of treatment continuously sooner or later.Observe every patient's skin lesion keratinization degree and skin lesion inflammation degree, calculate the meansigma methods of every group of above-mentioned two indexs of patient, table 1 is seen in result's contrast.
Table 2
| The treatment group | Matched group | Blank control group | |
| Skin lesion keratinization degree (%) | 9% | 35% | 58% |
| Skin lesion inflammation degree (%) | 23% | 32% | 50% |
Can find out that from table 2 lithium chloride solution of present embodiment is more obvious to the curing psoriasis effect, especially to the symptom of Keratoderma, effect is remarkable.
Clinical trial 2: be directed against for 30 routine sick ages more than 2.5 years, the ichthyosis patient that the state of an illness is similar establishes the treatment group: 10 examples, the tanshinone solution of obliterating present embodiment; Matched group: 10 examples, obliterating U.S. tinea clear (purchasing Rong Yuan Bioceuticals Inc.) in Xi'an; Blank control group: 10 examples, obliterating normal saline.Three groups Therapeutic Method is: dip in disinfecting cotton swab and get smear, directly be coated onto the ichthyosis affected area, every day 2 times, 30 days course of treatment, use 4 courses of treatment continuously.Observe every patient's skin lesion keratinization degree, the result shows that the treatment group has 6 example recoveries from illness, and 3 routine Keratoderma degree alleviate 70%, 1 routine Keratoderma degree and alleviate 40%; Matched group 2 example recoveries from illness, 4 routine Keratoderma degree alleviate 50%, 4 routine Keratoderma degree and alleviate 30%; Blank control group 2 routine Keratoderma degree alleviate the no significant change of 20%, 5 example, and the 3 routine keratinization degree that remain increase the weight of.The lithium chloride solution that present embodiment is described is obvious to treatment ichthyosis effect, has confirmed that lithium chloride can effectively suppress keratinocyte propagation.
The above only is a preferred implementation of the present invention; Should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the inventive method; Can also make some improvement and replenish, these improvement and replenish and also should be regarded as protection scope of the present invention.
Claims (4)
1. lithium chloride suppresses the application in the keratinocyte hyperproliferation disease medicine in preparation.
2. application according to claim 1 is characterized in that, described cell hyperproliferation disease is a psoriasis.
3. application according to claim 1 is characterized in that, described cell hyperproliferation disease is an ichthyosis.
4. application according to claim 1 is characterized in that, described cell hyperproliferation disease is the keratinocyte tumor.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1980681A (en) * | 2004-07-09 | 2007-06-13 | 新加坡科技研究局 | Modulation of GSK-3beta and method of treating proliferative disorders |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1980681A (en) * | 2004-07-09 | 2007-06-13 | 新加坡科技研究局 | Modulation of GSK-3beta and method of treating proliferative disorders |
Non-Patent Citations (2)
| Title |
|---|
| 李琨等: "氯化锂对MGC803细胞增殖及细胞周期的影响", 《科学技术与工程》, vol. 9, no. 17, 30 September 2009 (2009-09-30), pages 5105 - 5108 * |
| 沈智等: "氯化锂对人肝癌细胞增殖和荷肝癌小鼠肿瘤生长抑制作用", 《实验动物与比较医学》, vol. 26, no. 2, 31 December 2006 (2006-12-31), pages 83 - 104 * |
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