I-dyslipidemia kwisifo sikashukela isimo lapho igazi lesiguli liqukethe okuqukethwe okuphakeme kwama-lipoprotein nama-lipids.
Ukweqile kwalezi zinto kuyingozi ngoba kukhulisa amathuba okusebenza okungafanele emsebenzini wesistimu yethambo yegazi, okuvame ukuholela ekubonakala kwe-atherossteosis. Ukugcwala okukhulu kwe-cholesterol kunomthelela ekubonakala kwe-pancreatitis eyingozi.
I-Hyperlipidemia ivame ukuhlotshaniswa nesifo sikashukela. Isimo somtholampilo salesi simo sifana nezibonakaliso ze-cardiac pathologies kanye ne-atherosclerosis. Ungayithola ngemuva kokuhlolwa kwelebhu.
I-Dyslipidemia: yini, izici zokuthuthuka zesifo sikashukela
Ama-lipoprotein angama-macromolecular, eziyindilinga eziyinkimbinkimbi ezithwala amaprotheni ahlukahlukene nama-lipids kuma-plasma egazi. Ama-Hydrophobic triglycerides ahlangana nama-cholesterol ester molecule akha umgogodla wama-lipoprotein, ozungezwe amaprotheni we-amphipathic nama-phospholipids.
Umgogodla we-lipoproteins uthwala ama-100-5000 cholesterol estres nama-molecule we-triglyceride. Amaprotheni angaphezulu ama-lipoprotein angama-alo-lipoprotein. Abadedeli kuphela i-lipid kusuka ku-nucleus, kodwa futhi babamba iqhaza ekuthuthweni kwe-lipoprotein kanye nokulawulwa kokugxila kwe-plasma lipid.
I-Apolipoprotein B100 iyadingeka ekwenzeni ama-lipoprotein e-hepatic of densities ahlukene (aphansi, aphakathi nendawo, aminyene). U-Zin B 48 unesibopho sokungena kwama-chylomicrons kusuka emathunjini. Futhi i-ApoA-1 yiprotheni ehamba phambili yokwakheka kwe-HDL.
IDyslipidemia kuhlobo 2 sikashukela ibangelwa izici eziningi:
- I-metabolism engakhokhisiwe.
- Obese.
- Ukusabela okungekuhle ngemuva kokuthatha umthamo omkhulu wezidakamizwa ezithile (i-beta-blockers, diuretics, androgens, systemic corticosteroids, progestins, immunosuppressants, AIPs).
- I-hyperlipidemia ye-Hereditary.
- Izifo ezihambisanayo (kaningi nesifo sikashukela - lokhu kuyi-hypothyroidism).
Kungani ushukela ephazamisa i-lipoprotein kanye ne-chylomicron metabolism? Ngemuva kokudla, ama-triglycerides (amafutha okudla) kanye ne-cholesterol adonswa yisisu esincane bese ethulwa engxenyeni ye-chylomicrons engena ohlelweni lwe-lymphatic, nangemva kokuba efakiwe ekujikelezeni ngokusebenzisa i-vena cava ephakeme.
Embhedeni we-capillary, i-chylomicron kanye ne-adipose izicubu zemisipha zibopha ama-enzymes we-lipoprotein lipase. Ngenxa yalokhu, kukhululwa ama-asidi wamafutha wamahhala.
Ama-FFA athunjwa ngama-adipocytes, lapho avela futhi ekwakhiweni kwama-triglycerides. Uma umsipha ubanjwe yi-FFA, khona-ke uyawusebenzisa njengomthombo wamandla, oxhumeka kwi-intracellular metabolism.
Izinsalela (izinsalela ze-chylomicron) ziwumkhiqizo wenqubo ye-lipolytic elahlekelwe cishe ama-75% we-triglycerides, okwenziwa ngokushesha kwisibindi.
PL - hepatic lipase (triglyceride), i-hydrolyzing triglycerides yezinsalela ze-chylomicron, isabandakanyeka ekuqedeni izinsalela. Kuhlobo 2 sikashukela i-mellitus, ukungasebenzi kahle kumetabolism yezinsalela zez holomicron kanye nama-chylomicrons kuvame ukwenzeka. Ngaphezu kwalokho, ngale ndlela ye-hyperglycemia engapheli, umsebenzi we-LPL uyancishiswa.
Kodwa-ke, ukumelana ne-insulin kuvuselela ukwakheka kwama-chylomicrons emathunjini. Endabeni yesifo sikashukela sohlobo loku-1, ukuphazamiseka kwesayensi ye-lipid kwenzeka kuphela ngokubola kwesifo. Lokhu kuboniswa ukwehla okukhulu komsebenzi we-Ll, okuhambisana nokukhuphuka okunamandla kwesamba se-triglycerides ngemuva kokudla.
I-Hyperlipidemia ingenzeka futhi ngenxa yesifo esinqunyiwe ngofuzo. IVLDLP ikhiqizwa isibindi, i-cholesterol kanye nama-estiglycerides esters, kanti ama-phospholipids kanye nama-moculethi angama-100 asemhlabeni.
Ukukhiqizwa kwe-VLDL esibindini kukhuthazeka ukuqothuka okuphezulu kwe-FFA kwezicubu zabo ze-adipose. Kodwa ukwakheka okuthuthukile esibindini se-cholesterol ne-FFA kushukela elinganciki i-insulin nakho kuyenzeka, yingakho ukukhiqizwa kweVLDL nakho kuyanda.
Ama-Triglycerides e-VLDL ku-plasma ahanjiswa ngogesi ku-LPL, aguqulwa abe yi-LSPP emincane futhi emincane ne-VLDL. Kuyaphawuleka ukuthi ama-LPP afana nezinsalela ze-chylomicron, kepha ziyehluka ngoba, ngaphezu kokusetshenziswa esibindini, afakwa egazini ku-LDL. Ngakho-ke, umsebenzi we-LPL uhlinzeka ngomsebenzi ojwayelekile we-metabolic oqala kusuka ku-VLDL, udlula STD, uphela nge-LDL.
I-ApoVUO ukuphela kwamaprotheni akhiwe ngaphezulu kwe-LDL okuyi-ligand ye-LDL receptors. Ngakho-ke, okuqukethwe kwe-LDL esegazini kuya ngezinto ezimbili:
- ukutholakala kwama-LDL receptors;
- Imikhiqizo ye-LDL.
Ngohlobo 2 sikashukela, i-VLDL triglycerides ivame ukukhuphuka. Ukuqina okukhulayo kwe-cholesterol nge-LDL ku-hyperglycemia engapheli kuchazwa ngokuqukethwe kwayo okukhulayo kuzinhlayiya ngazinye ze-lipoprotein.
I-Peroxidation noma i-glycation ye-LDL kuholela ekungasebenzi kahle kokuqedwa okujwayelekile kwezinhlayiya ze-lipoprotein, okuholela eqinisweni lokuthi baqala ukuqoqa ezindongeni ze-vascular. Ngaphezu kwalokho, i-insulin ivusa ukubonakaliswa kohlobo lwe-LDL receptor gene, futhi, ngenxa yalokho, ukumelana ne-insulin noma ukuntuleka kwama-hormone nakho kungathinta kabi i-metabolism ye-LDL.
I-HDL isakhiwo esiyinkimbinkimbi. Izinhlayiya zokuqala zibizwa nge- prebeta-HDL. Lawa amukela i-cholesterol yeselula yamahhala, ngakho-ke i-HDL isinyathelo sokuqala sokuhambisa i-cholesterol esibindini nakwezicubu zephutha, lapho iphuma khona nomzimba.
Ama-cholesterol esters nawo angaba yingxenye yezinhlayiya ze-VLDL nama-chylomicrons lapho kunamaprotheni e-cholesteryl ester transport. Kuhlobo 2 sikashukela i-mellitus, inkomba ye-HDL-C ivame ukwehliswa ngenxa yokunyuka kokuhamba kwe-cholesterol ester kusuka ku-HDL kuye ku-HDL.
Kodwa-ke, ngesifo sikashukela sohlobo 1, i-HDL-C ihlala ijwayelekile noma i-overestimated.
Imigomo ejwayelekile yokwelashwa
Ukwelashwa kwe-dyslipidemia yesifo sikashukela kusekelwe ezimisweni ezintathu eziholayo. Lokhu kungukuphatha ushukela wegazi, ukwehla kwesisindo nokudla.
Ohlelweni lwesibili sikashukela, ukudla okulula ama-carbohydrate, i-cholesterol namafutha agcwele kufanele kube nomkhawulo. Kumenyu yansuku zonke, kuyinto efiselekayo ukufaka imikhiqizo equkethe ama-acid ama-monounsaturated acid ne-fiber yokudla, ngaleyo ndlela ithuthukise iphrofayili ye-lipid.
Uma isifo sikashukela silwa ngenkuthalo nesisindo ngokweqile, khona-ke ukugcwala kwama-triglycerides egazini lakhe kuzokwehla ngo-18%, kanti nama-antibodies e-cholesterol-cholesterol-okwehlayo azokwehla ngo-8%.
Kuyaqapheleka ukuthi ngesifo sikashukela esingancikeli i-insulin, ukuthatha izidakamizwa ezinciphisa ushukela, kufaka ne-insulin eyengeziwe, kuphela okubuyisela kancane okujwayelekile amazinga e-metabolism.
Ngakho-ke, iMetformin inganciphisa kuphela i-pligma triglycerides ifike ku-10%, iPioglitazone - ifike ku-20%, kanti iRosiglitazone ayinawo umthelela ekusebenzeni kwe-lipid. Ngokuphathelene ne-LDL-C, izidakamizwa ezinciphisa ushukela zithinta le nqubo kanjena:
- I-Metformin yehlisa ngo-5-10%;
- I-pioglitazone inyuka ngo-5-15%;
- I-Rosiglitazone inyuka ngo-15% noma ngaphezulu.
Ukwelashwa kwe-insulin kunomthelela ekwehleni okuncane kwe-LDL-C. Futhi ama-sulfonamides awanawo umphumela obalulekile we-lipid metabolism.
Kuhlobo 1 sikashukela, ukwelashwa kwe-insulin okunamandla kunganciphisa kakhulu i-plasma LDL-C kanye ne-triglycerides. Kodwa-ke, izinga lesinxephezelo se-lipid metabolism alithinti i-HDL-C ngendlela yesibili yesifo sikashukela.
Ama-Sulfanilamides ukuthi ushukela wegazi ophansi awakuthinti ukuhlangana kwe-HDL-C. Kodwa-ke, iMetformin, ngenxa yokwehla kwe-triglycerides, inyusa i-HDL-C, kodwa hhayi kakhulu.
I-pioglitazone neRosiglitazone inyusa i-HDL-C ezigulini ezinesifo sikashukela sohlobo 2. Ngakho-ke, ukuze i-metabolism e-normalization ibe ngokwejwayelekile kuma-diabetesics angaxhomekeki e-insulin, ukwelashwa okwehlisa i-lipid kuyadingeka. Futhi esimweni sohlobo lokuqala sikashukela, kuyadingeka ukufezekisa isinxephezelo se-carbohydrate metabolism.
I-Hypolipidemia in sikashukela siphathwa ngama-statins kanye nezinye izidakamizwa, ezibandakanya iNiacin, i-SCF, i-Fenofibrate, i-Ezetimibe. Izidakamizwa ezinjalo zinciphisa i-cholesterol ye-LDL.
Ukwandisa i-HDL-C, kusetshenziswa i-fibrate ne-nicotinic acid, okuvumela ukwehlisa inani le-triglycerides. IGemfibrozil, Fenofibrate, futhi neNiacin kufanele yabelwe eqenjini lesibili. Uma izinga le-LDL-C liphezulu kakhulu, khona-ke imithamo ephezulu yama-statin inikezwa onesifo sikashukela.
I-hyperlipidemia ehlanganisiwe iqedwa ngezindlela ezintathu:
- umthamo okhuphukile wama-statins;
- inhlanganisela ye-satin enemicu;
- inhlanganisela yama-satins nge-niacin.
Izizathu zokwelashwa okuphelele kokuncipha kwe-lipid okufanele zenziwe ziyahlukahluka. Okokuqala, le ndlela isehlisa ngempumelelo i-LDL-C ne-LDL-C.
Okwesibili, ukwelashwa okuxubile kwehlisa amathuba okuphendula okungekuhle futhi kunciphise i-cholesterol-LDL ehambisana nokuthatha i-fibrate.
Okwesithathu, le ndlela ivumela ukusetshenziswa kwe-SCLC ezigulini ezine-hypertriglyceridemia kanye nenkomba ye-overestimated ye-LDL-C.
Amaqembu ezidakamizwa ezisetshenziselwa i-dyslipidemia
Kunemikhakha emi-3 yezidakamizwa ezithinta i-lipoproteins ye-plasma. Lawa ama-inhibitors we-HMG-COA reductase inhibitors, abahleli ngokulandelana kwama-asidi acid, imicu fibrate.
Izimo zivame ukusetshenziselwa ukwehlisa ukuqoqwa kwe-LDL-C, ngakho-ke kunqunyelwe i-hyperlipidemia. I-Pravastatin, i-Simvastatin, iLovastatin ngama-metabolites of fungi noma ama-metabolites. Futhi iRosuvastatin, Atorvastatin, Fluvastatin izidakamizwa zokwenziwa.
I-Simvastatin neLovastatin zithathwa njenge- "pro-agents", ngoba zinomphumela wokwelapha kuphela ngemuva kwe-hydrolysis esibindini. Futhi amanye ama-statin akhululiwe ngesimo esisebenzayo.
Umgomo wokusebenza kwe-HMG-COA reductase Inhibitors ukuthi bacindezela i-enzyme ebalulekile ye-cholesterol synthesis. Ngaphezu kwalokho, la ma-ejenti anciphisa ukukhiqizwa kwe-Apo B100, okwenza kusebenze ama-LDL receptors futhi afake ama-lipoprotein. Lokhu kuholela eqinisweni lokuthi ukugcwala kwama-triglycerides e-VLDL, i-cholesterol ye-LDL, kwehla ngokungazelele egazini.
I-Pharmacokinetics yama-statins:
- ukumunyiswa kusuka kuma-30 kuye kuma-90%;
- eyenziwe ngesibindi isuka ku-50 iye ku-79%;
- okukhishwa ngaphezulu yizinso.
Ngokusebenzisana kwama-statins nge-FFA, ukumunca kwabo kuyancipha. Futhi, umphumela ofanayo uyaphawulwa ngokuhlanganiswa kwezidakamizwa ezibanga umphumela we-myopathic weLovastatin.
Ngaphezu kwalokho izinkomba zeLovastatin, atorvastatin neSimvastatin zizokhuphuka ngemuva kokuphuza ujusi we grapefruit. Ngokwazisa kweWarfarin neRosuvastatin, ukwanda kwesenzo se-prothrombin kwenzeka.
Ngomthamo wansuku zonke we-10-40 mg, i-HMG-COA reductase inhibitors yehlise i-cholesterol ye-LDL ema-50% futhi ikhuphule i-HDL-C ngo-5-10%.
Izitifiketi zikhonjiswa kwabanesifo sikashukela nge-TG ekhuphuke ngokulinganisela kanye ne-cholesterol ephezulu ye-LDL. Zivimbela nokwakhiwa kwama-gallstones, okubaluleke kakhulu kwi-neuropathy yesifo sikashukela.
I-Myositis yindlela yokusabela ejwayelekile kakhulu ngemuva kokuthatha ama-statins, kepha akuvamile ukuba ikhule. Ukuphendula okungafani njengoku:
- ukuqunjelwa
- i-arthralgia;
- Ubuhlungu besisu
- i-dyspepsia kanye nesifo sikashukela;
- ukuqaqamba kwemisipha.
Ama-sequence we-Bile acid angama-resins abopha ama-bile acid emathunjini. Izidakamizwa ezinjalo zehlisa i-LDL-C ziye kuma-30% ngokuguqula okuqukethwe kwe-HDL. Ngokunokwenzeka, ama-SCFA angakhulisa ama-triglycerides.
Ekwelapheni i-dyslipidemia ngesifo sikashukela i-mellitus, ukusebenza ngempumelelo kwe-bile acid sequestrants kuyafana nesenzo sama-statins, kepha kusetshenziswa kuphela okuhlangene kwale mithi. I-SCFA igxilwa ngamanani amancane emathunjini. Umphumela wokwelapha unqunywa izinga lokunciphisa cholesterol, eliziveza emavikini angama-2-3.
Ama-SCFA athinta ukufakwa kwezidakamizwa eziningi, kufaka phakathi izindlela zokuvimbela inzalo ngomlomo, ama-antiarrhythmic nama-anticonvulsants. Ngakho-ke, ezinye izimali kufanele zithathwe kuphela ngemuva kokuthi kudlule amahora angu-4 ngemuva kokuthatha i-SCFA.
Izicucu ze-Bile acid zisetshenziselwa ukuqeda i-hypercholesterolemia. Kodwa njengoba lesi sigaba semithi singavusa ukwanda kokuxineka kwe-triglyceride, kubalulekile ukulawula le nkomba ngesikhathi sokwelashwa. Ngakho-ke, i-SCFA akufanele ithathwe ezigulini ezine-hyper-triglyceridemia.
Imvamisa, ngemuva kokuthatha i-SCFA, ukuqunjelwa kanye nokuphazamiseka kwezifo ezinqubuka emzimbeni. Awukwazi ukuhlanganisa ukudla kwabo ne-sulfonamides nezinye izidakamizwa, ubona ikhefu lehora lesithupha. Ama-SKHK afakwa ku-contraindication lapho kukhona amatshe ku-blallder, i-gastrointestinal kanye ne-biliary.
Izithako ze-Fibric acid ezifana ne-Hem fibrosyl neFenofibrate zingama-agonist we-PPAR alpha agonists. Izidakamizwa ezifanayo zesifo sikashukela zinomphumela onamandla we-lipid metabolism, zinciphisa amathuba okuba nezinkinga zenhliziyo. Ngakho-ke, i-fibrate yehlisa i-cholesterol-LDL iye kuma-20%, ama-triglycerides - aze afike ku-50%, futhi izinga le-cholesterol-HDL lenyuka ngo-10-20%.
Kuyaphawuleka ukuthi i-fenofibrate iyindlela ehlukile ekwelapheni ukugxila okuphezulu kwe-LDL-C kubantu abanesifo sikashukela bethatha ama-statin ababengenamphumela oyifunayo.
Amafabhethi athinta i-lipid metabolism kushukela, okuvela ngokwandayo:
- lipoprotein lipase;
- I-ABC-A1;
- I-Apo A-P ne-apo A-1 (amaprotheni amakhulu we-HDL).
Ama-Fibrate futhi anciphisa ukuvezwa kweprotheni yokulimaza i-cholesterol futhi kunciphise i-apo C-III. Futhi, izidakamizwa zikhulisa i -apo A-V, ukukhiqizwa kwayo kwehlisa inani lama-lipoprotein, ngenani elikhulu le-TG.
Ngaphezu kwalokho, i-fibrate esters inhibit lipogenesis esibindini. Baxhumana ne-hepatic X receptor, evimbela i-PCR-mediated lipogenesis. Ama-Derivatives e-fibric acid nawo anomphumela we-antiatherogenic.
Kodwa-ke, ama-ejenti okuhola e-dyslipidemia angama-statins, kanti imicu imiselwe ushukela othembela ku-insulin, kuphela kulezi ziguli ezingakwazi ukubekezelela le mithi. Ukwelashwa okuhlangene kwama-fibrate, kunconywa ukusetshenziswa kwe-fenofibrate.
Kuyaqapheleka ukuthi le mishanguzo ingabekwa ukuthi inciphise i-LDL nge-TG ephansi kakhulu. Kepha kulokhu, izidakamizwa ezivela kwamanye amaqembu zivame ukusetshenziswa, njenge-SCFA, i-nicotinic acid nama-statin.
Isikhathi esiphakathi sokwelashwa kwe-fibrate izinyanga ezingama-3-6. Njengoba le mishanguzo ikhulisa amathuba okuba ne-cholelithis, akufanele isetshenziswe yisifo sikashukela nge-autonomic neuropathy.
Isifo sikashukela esine-nephropathy kanye neziguli esezikhulile kufanele sisebenzise imicrate ngokucophelela kakhulu, ngoba zisuswa kakhulu izinso. Ngesikhathi sokukhulelwa nangesikhathi sokukhulelwa, ukwelashwa nalawa ma-ejenti akuvunyelwe.
Imiphumela emibi ejwayelekile yokuthatha i-fibrate yile:
- ukuthopha;
- isicanucanu
- ukungasebenzi kwe-erectile;
- Ubuhlungu besisu
- imivimbo yesikhumba;
- ukuhlanza
- isifo sohudo
- Isiyezi
- ukuqunjelwa kanye nezinto.
Ngaphezu kwama-statins, ama-SCFA kanye nama-fibrate, we-hyperlipidemia, akhula ngokuma kwesifo sikashukela emva kweminyaka engama-50, i-nicotinic acid ingabekwa. Lesi kuphela i-lipid yehlise i-lipid eyehlisela i-lipoprotein, kepha inemiphumela emibi eminingi.
Futhi, udokotela angabeka ama-omega-3 fatty acids ukunciphisa i-hypertriglyceridemia. Ngaphezu kwalokho, i-OZHK inciphisa ingozi yezinkinga zenhliziyo futhi ibe nomphumela we-antiatyrogenic. Ividiyo ekulesi sihloko izokutshela ukuthi ungazelapha kanjani iziphazamiso zemetabolism ye-lipid.
