Fibroz is a consolidation of a connecting fabric with the advent of cicatricial changes in the various bodies, arising, as a rule, as a result of a chronic inflammation. About a clinical picture of dofibrotichesky changes (on an example фиброза to a liver) has told on the next symposium which has passed in a framework of All-Russia the Internet of the Congress of experts in internal diseases, the doctor of medical sciences, Alexey Olegovich Buyeverov.
«Fibroz - result of long change of a fabric, - has made a reservation at once Alexey Olegovich. - Therefore especially as its important characteristics the stage and speed of pathological process» act.
Change ekstratsellyulyarny матрикса at фиброзе a liver is characterised:
- increase at 3-10 time of ETsM components
- increase in fibrilobrazuyushchy types of collagen (I and III)
- change of structure of molecules
- vaskulyarizatsiya синусоидов
- pereraspredelniy матрикса
1. Initiation. Activation of zvezdchaty cages as a result of parakrinny stimulation by the next cellular populations (гепатоциты, endoteliya синусоидов, Kupffer's cells, тромбоциты). Damaged гепатоциты (cages паренхимы a liver) - AFK source that stimulates Kupffer's cells.
- Proliferatsiya. PDGF (a trombotsitarny factor of growth) - the strongest mitogen of zvezdchaty cages. The mechanism митогенеза is realised by means of activation фосфоинозитол - a 3-kinase and some other enzymes.
- Hemotaksis. Zvezdchatye cages are capable to migration in the direction of the greatest concentration of hemoattraktant (PDGF, MCP-1, CXCR3). From 19 identified hemokinovy receptors 9 are localised on zvyozdchaty cages. Unique from them, possessing potential antifibrotichesky effect - CXCR3. Adenozin suppresses хемотаксис.
- Collagen production. Zvezdchatye cages breed and increase production матрикса. The collagen I which production increases under the influence of TGF?1 is most studied. CTGF/CCN2 (a factor of growth of a connecting fabric) - potential profibrogenny цитокин which concentration is regulated by a glikemiya and an insulinemiya.
- Sokratimost. Is defined by an expression of a cytoskeletal protein. The main regulators - endotelin-1 and nitrogen oxide, additional - angiotensin II, эйкозаноиды (the oxidised derivatives of polynonsaturated fat acids), predserdny natriyureticheskiya пептид, соматостатин, carbon monooxide.
- Degradation матрикса. Fibrogenez is defined by balance between production and degradation матрикса.
- Loss ретиноидов
- Emission tsitokinov/hemokinov
Fibrogenez at chronic virus hepatitises.
For patients with chronic hepatitis B and C are characteristic:
- Strengthening ангиогенеза (PDGF)
- Raised expression MMP-2
- Proliferatsiya of Ito's cells (C4, collagen IV, актомиозин)
Successful etiotropny therapy causes
- Decrease in proliferativny activity of cells of Ito, фибробластов, ангиогенеза
- Increase of expression MMP-7 and MMP-9
- Strengthening of antimetalloproteinazny activity
Range of biological effects:
- Anti-depressive effect
Influence on cytoclinical balance and NO exchange:
- suppression of production pro-inflammatory цитокинов
- strengthening of production of IL10
- suppression indutsibelny NO сингазы
Influence on фиброгенез: present and future.
- Etiotropny preparations are most effective in this regard, but they possess the mediated antifibrogenny effect
- Pathogenetic treatment (адеметионин, силимарин, UDHK, the preparations influencing activity of zvezdchaty cages).
Photo from a site http://evanmed.ru