Use of LCAT in preparing drug for treating and/or preventing hepatic bone disease

A technology of use and medicine, applied in the field of treatment and prevention of osteoporosis or osteomalacia, to achieve the effect of preventing and treating hepatic bone disease, broadening the field of choice, and relieving osteoporosis

Active Publication Date: 2018-11-02
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there is no report about LCAT in the treatment of hepatic bone disease

Method used

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  • Use of LCAT in preparing drug for treating and/or preventing hepatic bone disease
  • Use of LCAT in preparing drug for treating and/or preventing hepatic bone disease
  • Use of LCAT in preparing drug for treating and/or preventing hepatic bone disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1. Construction of primary osteoblast / primary osteoclast and primary liver parenchymal cells co-culture system

[0025] Implementation method: Add the isolated primary osteoblasts / primary osteoclasts into a microporous filter culture chamber (MerckMillipore, USA), add NBD fluorescently labeled cholesterol and incubate for 24 hours, then wash off the unphagocytosed cells with PBS solution. NBD fluorescently labeled cholesterol outside primary osteoblasts / primary osteoclasts. The primary hepatic parenchymal cells were transferred to the lower layer of the microporous membrane culture chamber. According to different treatments, the microporous membrane culture chamber system was divided into three groups, namely PBS treatment group, exogenous rLCAT treatment group (100ng / ml), CCl 4 Pre-injury liver parenchymal cell group (1mM), the treatment method is as follows:

[0026] PBS treatment group: PBS solution was added to both the upper layer cells and the lower laye...

Embodiment 2

[0031]Example 2. The expression of LCAT in mice with hepatic bone disease and the relationship between the expression of LCAT and bone mineral density in patients with hepatic bone disease

[0032] In order to verify the expression of LCAT in mice with hepatic bone disease and whether there is a certain relationship between the expression of LCAT and bone mineral density in patients with hepatic bone disease, we constructed a mouse model of hepatic bone disease and collected hepatic bone disease Patient serum and measured bone density data.

Embodiment 3

[0035] Example 3. Effect of LCAT on osteoblasts and osteoclasts

[0036] Implementation method: extract osteoblasts from the skull of 6-day-old male mice (C57BL / 6), extract osteoclast precursors from the bone marrow cavity of the lower limbs of 6-week-old male mice (C57BL / 6), and induce mature osteoclasts with Rank1, Add 200ng / ml exogenous rLCAT solution into the two kinds of cells, and add an equal volume of PBS solution to the control group, incubate the cells in each group for 24 hours, extract RNA, and detect the biological markers of osteoblasts by real-time quantitative PCR Objects Runx2, Ocn and Sp7 ( image 3 A-C in the figure), and osteoclast biomarkers CTSK, Trap and OSCAR ( image 3 D-F graph in ) expression level.

[0037] Example result: as image 3 As shown, after the exogenous rLCAT solution was added to osteoblasts and osteoclasts and incubated for 24 hours, the expression levels of osteoblast-related markers Runx2, Ocn and Sp7 were significantly increased c...

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PUM

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Abstract

The invention belongs to the field of biomedicine, and particularly relates to use of lecithin-cholesterol acyltransferase (LCAT) in preparing a drug or a healthcare product for treating and / or preventing the hepatic bone disease. According to the cell and animal experiments, the LCAT can realize reverse cholesterol transport of from osteocyte to hepatocyte, so that osteoporosis is relieved; meanwhile, an abnormal skeletal system in a chronic cirrhosis process further can be relieved, and bone density is increased, so that a brand-new choice and idea is provided for treating chronic hepatic bone disease, and the LCAT has a potential clinical application prospect.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to the use of lecithin-cholesterol acyltransferase (LCAT) in the preparation of medicines or health products for treating and / or preventing hepatic bone disease, and in treating and preventing osteoporosis or osteomalacia. Background technique [0002] As the metabolic center of the body, the liver is an important metabolic organ to maintain the body's homeostasis. A large number of liver cells not only undertake the function of digestion and detoxification, but also secrete a large number of cytokines. play an important regulatory role. Similarly, as another important organ of the human body—skeleton, in addition to exerting stress support and motor functions, it can also regulate the body's immunity through the secretion of regulatory factors, and regulate the body's homeostasis by affecting the body's glucose metabolism balance. At present, the regulation of liver to bone h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/45A61P19/08A61P19/10
CPCA23V2002/00A61K38/45A23L33/00C12Y203/01043A23V2200/306
Inventor 薛斌蒋青陆克石天舒
Owner NANJING UNIV
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