значение медико-генетических факторов в объективной оценке
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Âåñòíèê Ñàíêò-Ïåòåðáóðãñêîãî óíèâåðñèòåòà. Ñåð. 11, 2006, âûï. 3 ÓÄÊ 616.089+616.379-008.64 Â.Â. Ïåòðîâà1, Þ.Ô. Êóëèêîâ1, Â.È. Ëàðèîíîâà2, Þ.À. Ñïåñèâöåâ2 1 Ñ.-Ïåòåðáóðãñêèé ãîñóäàðñòâåííûé óíèâåðñèòåò, ìåäèöèíñêèé ôàêóëüòåò 2 Ñ.-Ïåòåðáóðãñêàÿ ãîñóäàðñòâåííàÿ ïåäèàòðè÷åñêàÿ ìåäèöèíñêàÿ àêàäåìèÿ ÇÍÀ×ÅÍÈÅ ÌÅÄÈÊÎ-ÃÅÍÅÒÈ×ÅÑÊÈÕ ÔÀÊÒÎÐΠ ÎÁÚÅÊÒÈÂÍÎÉ ÎÖÅÍÊÅ ÄÅÑÒÐÓÊÒÈÂÍÛÕ ÎÑËÎÆÍÅÍÈÉ ÑÈÍÄÐÎÌÀ ÄÈÀÁÅÒÈ×ÅÑÊÎÉ ÑÒÎÏÛ Ïî äàííûì ÂÎÇ â ìèðå íà ñåãîäíÿøíèé äåíü íàñ÷èòûâàåòñÿ áîëåå 150 ìëí áîëüíûõ ñàõàðíûì äèàáåòîì, èç êîòîðûõ 8090% ñîñòàâëÿþò ïàöèåíòû ñ èíñóëèííåçàâèñèìûì äèàáåòîì. Çà ïîñëåäíåå äåñÿòèëåòèå áîëåå ÷åì â ïÿòü ðàç óâåëè÷èëàñü ÷àñòîòà ðàçâèòèÿ òàêîãî òÿæåëîãî îñëîæíåíèÿ, êàê ñèíäðîì äèàáåòè÷åñêîé ñòîïû (ÑÄÑ), ÷òî ñâÿçàíî, ïî-âèäèìîìó, ñ óâåëè÷åíèåì ïðîäîëæèòåëüíîñòè æèçíè áîëüíûõ.  òî æå âðåìÿ ÷àùå âñòðå÷àþòñÿ íàèáîëåå òÿæåëûå ôîðìû ÑÄÑ, îáóñëîâëåííûå íàëè÷èåì õðîíè÷åñêîé ãèïåðãëèêåìèè è ïðîãðåññèðóþùåé ïîëèàíãèîíåéðîïàòèåé íèæíèõ êîíå÷íîñòåé. Ãíîéíî-íåêðîòè÷åñêèå ïîðàæåíèÿ ïðè CÄC ÿâëÿþòñÿ îñíîâíîé ïðè÷èíîé ãîñïèòàëèçàöèè è çàíèìàþò âåäóùåå ìåñòî ïî ïðîäîëæèòåëüíîñòè è ñòîèìîñòè âíóòðèáîëüíè÷íîãî ïðåáûâàíèÿ. Ãëàâíûìè ïðîáëåìàìè, ñ êîòîðûìè ñòàëêèâàþòñÿ õèðóðãè ïðè ëå÷åíèè ÑÄÑ, ÿâëÿþòñÿ: ìíîãîîáðàçèå âàðèàíòîâ êëèíè÷åñêîãî òå÷åíèÿ äåñòðóêòèâíûõ ïðîöåññîâ â íèæíèõ êîíå÷íîñòÿõ, èõ âîëíîîáðàçíîå òå÷åíèå, ïîÿâëåíèå âòîðè÷íûõ íåêðîçîâ ïîñëå ðàäèêàëüíûõ õèðóðãè÷åñêèõ âìåøàòåëüñòâ, ñëàáî ïîääàþùàÿñÿ êîððåêöèè ãëèêåìèÿ. Ââèäó òîãî, ÷òî îñíîâíàÿ ïðè÷èíà ñìåðòíîñòè îò ñàõàðíîãî äèàáåòà ñåðäå÷íî-ñîñóäèñòûå è öåðåáðîâàñêóëÿðíûå çàáîëåâàíèÿ, ñðåäè êîòîðûõ àòåðîñêëåðîç ñîñòàâëÿåò 65,9%, ìîæíî ãîâîðèòü î âçàèìîñâÿçè ðÿäà çâåíüåâ ïàòîãåíåçà ñàõàðíîãî äèàáåòà è àòåðîñêëåðîçà. Îñíîâíîå çíà÷åíèå â ïàòîãåíåçå ïîñëåäíåãî èìåþò íàðóøåíèÿ ëèïèäíîãî îáìåíà. Ðåçóëüòàòû áîëüøîãî êîëè÷åñòâà íàó÷íûõ èññëåäîâàíèé ïîäòâåðæäàþò ñâÿçü äèñëèïèäåìèé ñ àòåðîñêëåðîòè÷åñêèì ïîðàæåíèåì àðòåðèé íèæíèõ êîíå÷íîñòåé.  íàñòîÿùåå âðåìÿ ñóùåñòâóþò ìíîãî÷èñëåííûå äàííûå î ñâÿçè ãåíåòè÷åñêè èçìåíåííûõ âàðèàíòîâ (ìóòàöèè, ïîëèìîðôèçì) ãåíîâ ëèïèäíîãî ìåòàáîëèçìà ñ ðåãóëÿöèåé ðàçëè÷íûõ çâåíüåâ ïàòîãåíåçà àòåðîñêëåðîçà è àññîöèèðîâàííûõ ñ íèì çàáîëåâàíèé. Ìîæíî òàêæå ñ÷èòàòü, ÷òî äëÿ ðàçâèòèÿ ñîñóäèñòûõ îñëîæíåíèé äèàáåòà íåîáõîäèìî âëèÿíèå êàê âíåøíèõ (õðîíè÷åñêàÿ ãëèêåìèÿ), òàê è âíóòðåííèõ (ãåíåòè÷åñêèõ) ôàêòîðîâ. Ìîæíî ïðåäïîëîæèòü, ÷òî ó îïðåäåëåííîãî ÷èñëà ïàöèåíòîâ èìååòñÿ ãåíåòè÷åñêàÿ ïðåäðàñïîëîæåííîñòü, êîòîðàÿ ïîä âëèÿíèåì âíåøíèõ ôàêòîðîâ èíèöèèðóåò ðàçâèòèå ñîñóäèñòûõ îñëîæíåíèé. Îäíàêî ïàòîãåíåç ðàçâèòèÿ ñèíäðîìà äèàáåòè÷åñêîé ñòîïû íà ñåãîäíÿøíèé äåíü îñòàåòñÿ äî êîíöà íå âûÿñíåííûì. Êðîìå òîãî, ó õèðóðãîâ íåò åäèíîãî ìíåíèÿ î ïðè÷è- © Â.Â. Ïåòðîâà, Þ.Ô. Êóëèêîâ, Â.È. Ëàðèîíîâà, Þ.À. Ñïåñèâöåâ, 2006 73 íàõ ðàçíîîáðàçèÿ òå÷åíèÿ äåñòðóêòèâíûõ ïðîöåññîâ â íèæíèõ êîíå÷íîñòÿõ è íåò åäèíîé ëå÷åáíîé òàêòèêè â îòíîøåíèè èõ êîððåêöèè. Îñòàåòñÿ òàêæå íåâûÿñíåííîé âçàèìîñâÿçü ìåæäó âàðèàíòàìè òå÷åíèÿ ÑÄÑ ñ ìåòàáîëè÷åñêèìè è ìîëåêóëÿðíî-ãåíåòè÷åñêèìè ôàêòîðàìè. Ýòî îáñòîÿòåëüñòâî ñîçäàåò äîïîëíèòåëüíûå òðóäíîñòè êàê â ïðîãíîçèðîâàíèè, òàê è â äèàãíîñòèêå âàðèàíòîâ ðàçâèòèÿ ãíîéíî-íåêðîòè÷åñêèõ ïðîöåññîâ, à òàêæå â âîçìîæíîñòè ýôôåêòèâíîãî ëå÷åíèÿ ïîñëåäíèõ. Íè â çàðóáåæíîé, íè â îòå÷åñòâåííîé ëèòåðàòóðå íåò åäèíîé êëàññèôèêàöèè ñèíäðîìà äèàáåòè÷åñêîé ñòîïû. Òàê êàê ïîðàæåíèÿ íèæíèõ êîíå÷íîñòåé ðàçíîîáðàçíû ïî ýòèîëîãèè è ïàòîãåíåçó, àíàòîìè÷åñêîé ëîêàëèçàöèè, ãëóáèíå ïîðàæåíèÿ òêàíåé è ñîïóòñòâóþùèì îáñòîÿòåëüñòâàì, âêëþ÷àÿ íàëè÷èå èëè îòñóòñòâèå èíôåêöèè, íåîáõîäèìà êëàññèôèêàöèÿ, êîòîðàÿ ñî÷åòàëà áû â ñåáå íàèáîëåå çíà÷èìûå èç íèõ è ïîçâîëèëà áû ñ âûñîêîé ñòåïåíüþ âåðîÿòíîñòè ïðîãíîçèðîâàòü äàëüíåéøåå òå÷åíèå ÑÄÑ [1, 2]. Ïî ìíåíèþ K. Van Acker, C. De Block [2], êëàññèôèêàöèÿ ÑÄÑ äîëæíà óäîâëåòâîðÿòü íåêîòîðûì òðåáîâàíèÿì: òî÷íîñòè, ãèáêîñòè, ñïåöèôè÷íîñòè è ïðîñòîòå. Îíà äîëæíà áûòü òàêæå ïðèåìëåìîé äëÿ êîììóíèêàöèè ìåæäó âñåìè ñïåöèàëèñòàìè, âêëþ÷àÿ ñðåäíèé ìåäèöèíñêèé ïåðñîíàë, âðà÷åé îáùåé ïðàêòèêè è ñïåöèàëèñòîâ. Êëàññèôèêàöèÿ äîëæíà âêëþ÷àòü àíàëèç îäíîãî èëè áîëåå èç ñëåäóþùèõ ýëåìåíòîâ: èíôåêöèÿ, íåéðîïàòèÿ, ñîñóäèñòàÿ ïàòîëîãèÿ è ãëóáèíà ïîðàæåíèÿ òêàíåé ñòîïû. Íàèáîëåå èçâåñòíûå è øèðîêî ïðèìåíÿåìûå êëàññèôèêàöèè ñëåäóþùèå: Meggit/ Wagner, Gibbons, Frykbergs/Colemans, Forrests, Knightons, Van Acker/Peter Classification, the Texas Diabetic Wound Classification è Ten-Level Seattle Wound Classification System [3, 12]. Êàæäàÿ èç íèõ ðàçðàáàòûâàëàñü äëÿ äîñòèæåíèÿ ðàçëè÷íûõ öåëåé, ó÷èòûâàÿ ïðè ýòîì îäèí èëè íåñêîëüêî àñïåêòîâ ÑÄÑ. È ëèøü íåìíîãèå èç íèõ ïðåäñòàâëÿþòñÿ öåííûìè äëÿ ïðîãíîçèðîâàíèÿ èñõîäà ÑÄÑ. Íàèáîëåå ðàöèîíàëüíîé â êëèíè÷åñêîì àñïåêòå ñ÷èòàåòñÿ â íàñòîÿùåå âðåìÿ êëàññèôèêàöèÿ ÑÄÑ, ïðåäëîæåííàÿ íà 1-ì Ìåæäóíàðîäíîì ñèìïîçèóìå ïî äèàáåòè÷åñêîé ñòîïå (Íèäåðëàíäû, 1991), îïèñûâàþùàÿ ïàòîãåíåòè÷åñêèå àñïåêòû ÑÄÑ [13]. Îíà ïîìîãàåò îöåíèòü ïðåèìóùåñòâåííîå âëèÿíèå îäíîãî èç ïàòîãåíåòè÷åñêèõ êîìïîíåíòîâ è â ñîîòâåòñòâèè ñ ýòèì íàçíà÷èòü àäåêâàòíîå ëå÷åíèå â ìàêñèìàëüíî ðàííèå ñðîêè. K. Van Acker, C. De Block [2] ñðàâíèëè ïðîãíîñòè÷åñêèå âîçìîæíîñòè íåêîòîðûõ êëàññèôèêàöèé è óêàçûâàþò íà áîëüøóþ öåííîñòü îäíîìåðíîé êëàññèôèêàöèè Meggit/ Wagner, îïèñûâàþùåé òîëüêî ìåñòíûå ïðîÿâëåíèÿ íà ñòîïå.  ëèòåðàòóðå òàêæå ïðèâîäÿòñÿ íåêîòîðûå îòäåëüíûå, íå ñèñòåìàòèçèðîâàííûå êðèòåðèè, ïîçâîëÿþùèå ïðåäâèäåòü âûñîêóþ ñòåïåíü âåðîÿòíîñòè àìïóòàöèè ïîðàæåííîé êîíå÷íîñòè, íàïðèìåð äëèòåëüíîñòü çàáîëåâàíèÿ äèàáåòîì, áîëåå ÷àñòîå ïðèìåíåíèå àíòèáèîòèêîâ, ÷àñòûå ðåâàñêóëÿðèçèðóþùèå îïåðàöèè, ãàíãðåíîçíûé õàðàêòåð ïîðàæåíèÿ ñòîïû è äð. Íàì ïðåäñòàâëÿåòñÿ, ÷òî êëàññèôèêàöèÿ CÄC äîëæíà ïîìîãàòü íå òîëüêî ïðîãíîçèðîâàíèþ èñõîäà îñëîæíåíèé ïîñëåäíåãî, íî è îïðåäåëÿòü ëå÷åáíóþ òàêòèêó â îòíîøåíèè ïàöèåíòîâ, â äàííîì ñëó÷àå ìåòîäû êîìïëåêñíîãî õèðóðãè÷åñêîãî ëå÷åíèÿ.  íàñòîÿùåì èññëåäîâàíèè ìû õîòèì ïîêàçàòü âîçìîæíóþ âçàèìîñâÿçü äåñòðóêòèâíûõ ïðîöåññîâ â íèæíèõ êîíå÷íîñòÿõ ïðè CÄC ñ ãåíåòè÷åñêèìè è ìåòàáîëè÷åñêèìè ôàêòîðàìè, à òàêæå âûðàáîòàòü äëÿ êàæäîé ãðóïïû ïàöèåíòîâ îïòèìàëüíóþ õèðóðãè÷åñêóþ òàêòèêó. Ìåòîäû èññëåäîâàíèÿ. Çà ïåðèîä 19992004 ãã. íàìè îáñëåäîâàíû è ïðîëå÷åíû 1000 ïàöèåíòîâ ñ ðàçëè÷íûìè ôîðìàìè ãíîéíî-íåêðîòè÷åñêèõ îñëîæíåíèé ÑÄÑ, íàõîäÿùèõñÿ íà ëå÷åíèè â îòäåëåíèè ãíîéíîé õèðóðãèè ãîðîäñêîé êëèíè÷åñêîé áîëüíèöû ¹ 5. Âîçðàñò ïàöèåíòîâ 74 ñîñòàâèë îò 41 äî 90 ëåò, ñòàæ çàáîëåâàíèÿ èíñóëèííåçàâèñèìûì ñàõàðíûì äèàáåòîì (ÈÍÑÄ) êîëåáàëñÿ â ïðåäåëàõ 1015 ëåò. Äëÿ áîëåå ïîëíîãî ïðåäñòàâëåíèÿ î ïàòîãåíåçå ðàçâèòèÿ CÄC ìû ïðîâåëè èññëåäîâàíèå íåêîòîðûõ çíà÷èìûõ ìåòàáîëè÷åñêèõ ïîêàçàòåëåé. Ó âñåõ îáñëåäóåìûõ áîëüíûõ ìåòîäîì êèíåòè÷åñêîé èììóíîíåôåëîìåòðèè îïðåäåëÿëè êîíöåíòðàöèþ àïîëèïîïðîòåèíîâ ÀðîÀl è Àðî â ñûâîðîòêå êðîâè. Èììóíîõèìè÷åñêèì ìåòîäîì îïðåäåëÿëè ïðîöåíò ãëèêîçèëèðîâàííîãî ãåìîãëîáèíà (%ÍâÀlc). Óðîâåíü ãëþêîçû, îáùåãî õîëåñòåðèíà (ÕÑ), õîëåñòåðèíà ëèïîïðîòåèíîâ âûñîêîé ïëîòíîñòè (ËÏÂÏ), òðèãëèöåðèäîâ (ÒÃ), ìî÷åâèíû è êðåàòèíèíà, à òàêæå àêòèâíîñòü àìèëàçû è ëèïàçû îïðåäåëÿëè èììóíîôåðìåíòíûì ìåòîäîì. Ðàñ÷åòíûì ïóòåì ïîëó÷èëè êîýôôèöèåíò àòåðîãåííîñòè (ÊÀ), êîíöåíòðàöèþ õîëåñòåðèíà ëèïîïðîòåèíîâ íèçêîé (ÕÑ ËÏÍÏ) è î÷åíü íèçêîé (ÕÑ ËÏÎÍÏ) ïëîòíîñòè. Ó÷èòûâàÿ ãåíåòè÷åñêóþ ïðåäðàñïîëîæåííîñòü ê ôîðìèðîâàíèþ è òå÷åíèþ äåñòðóêòèâíûõ ïðîöåññîâ â íèæíèõ êîíå÷íîñòÿõ, ìû ïðîâåëè èçó÷åíèå ÷àñòîòíîãî ðàñïðåäåëåíèÿ àëëåëåé ãåíåòè÷åñêèõ âàðèàíòîâ (ìóòàöèé, ïîëèìîðôèçìîâ) «êàíäèäàòíûõ» ãåíîâ, àññîöèèðîâàííûõ ñ ðàçâèòèåì ñåðäå÷íî-ñîñóäèñòîé ïàòîëîãèè: Ñ677Ò ãåíà MTHFR, Å2/Å3/Å4 ãåíà ÀðîÅ), I/D ãåíà ÀÑÅ. Èçó÷åííûå ìîëåêóëÿðíî-ãåíåòè÷åñêèå ìàðêåðû ìîãóò áûòü ñâÿçàíû ñ ôàêòîðàìè ðèñêà ðàçâèòèÿ ñåðäå÷íî-ñîñóäèñòîé ïàòîëîãèè è ïðèíèìàòü ó÷àñòèå â ôîðìèðîâàíèè àíãèîïàòèè íèæíèõ êîíå÷íîñòåé, à èìåííî: ìóòàöèÿ Ñ677Ò ãåíà MTHFR ñâÿçàíà ñ ãèïåðãîìîöèñòåèíåìèåé, êîòîðàÿ èãðàåò çíà÷èòåëüíóþ ðîëü â ïîâðåæäåíèè ýíäîòåëèÿ ñîñóäîâ è ïðîâîöèðóåò ñêëîííîñòü ê òðîìáîçàì. Õîðîøî èçó÷åííûé I/D-ïîëèìîðôèçì ãåíà ÀÑÅ â ñâîþ î÷åðåäü àññîöèèðîâàí ñ ðàçâèòèåì àðòåðèàëüíîé ãèïåðòåíçèè è ÿâëÿåòñÿ âåäóùèì ôàêòîðîì ðèñêà ðàçâèòèÿ èøåìè÷åñêîé áîëåçíè ñåðäöà. Áîëåå ðåäêî âñòðå÷àþùèåñÿ àëëåëè ãåíà ÀðîÅ (Å4/Å2) àññîöèèðîâàíû ñ èçìåíåíèåì ñêîðîñòè êàòàáîëèçìà àïîëèïîïðîòåèíîâ, è èìåþòñÿ äàííûå î ñâÿçè íîñèòåëüñòâà ýòèõ àëëåëåé ñ ðàçâèòèåì àòåðîãåííûõ òèïîâ äèñëèïèäåìèé è ïðåäðàñïîëîæåííîñòüþ ê ðàçâèòèþ àòåðîñêëåðîçà. Âñå îáñëåäóåìûå áîëüíûå áûëè îáúåäèíåíû íàìè â òðè ãðóïïû, â çàâèñèìîñòè îò âàðèàíòîâ ïðîâîäèìîãî õèðóðãè÷åñêîãî ëå÷åíèÿ. Ïàöèåíòàì ïåðâîé ãðóïïû íå ïðîâîäèëèñü õèðóðãè÷åñêèå âìåøàòåëüñòâà, îíè ïîëó÷àëè òîëüêî êîíñåðâàòèâíóþ òåðàïèþ. Ïàöèåíòàì âòîðîé ãðóïïû ïðîèçâîäèëèñü ðàçëè÷íûå âàðèàíòû àìïóòàöèé íà óðîâíå ñòîïû. Òðåòüþ ãðóïïó îáðàçîâàëè ïàöèåíòû, ó êîòîðûõ ïðîèçâîäèëèñü àìïóòàöèè íà óðîâíå ãîëåíè è áåäðà. Ïî õàðàêòåðó äåñòðóêòèâíûõ ïðîöåññîâ â íèæíèõ êîíå÷íîñòÿõ ïàöèåíòû ðàñïðåäåëèëèñü ñëåäóþùèì îáðàçîì: ïåðâàÿ ãðóïïà èìåëà III ñòåïåíü ïîðàæåíèé ïî êëàññèôèêàöèè Âàãíåðà, âòîðàÿ ãðóïïà IIIIV ñòåïåíü, à ó òðåòüåé ãðóïïû îòìå÷àëàñü V ñòåïåíü ïîðàæåíèé íèæíèõ êîíå÷íîñòåé. Ðåçóëüòàòû èññëåäîâàíèÿ è èõ îáñóæäåíèå. Ïàöèåíòû âñåõ îáñëåäóåìûõ ãðóïï èìåëè ïîâûøåííûé óðîâåíü ãëèêîçèëèðîâàííîãî ãåìîãëîáèíà áîëåå 10%, ÷òî ñîîòâåòñòâîâàëî ñîäåðæàíèþ ãëþêîçû â ñûâîðîòêå êðîâè îêîëî 13,7 ììîëü/ë. Ó ïàöèåíòîâ ïåðâîé ãðóïïû îòìå÷àëàñü ñíèæåííàÿ êîíöåíòðàöèÿ ÀðîÀl â ñî÷åòàíèè ñ ïîâûøåííîé êîíöåíòðàöèåé Àðî è, òåì íå ìåíåå, ñîõðàíÿëñÿ áëèçêèé ê íîðìàëüíîìó óðîâåíü õîëåñòåðèíà ëèïîïðîòåèíîâ âûñîêîé ïëîòíîñòè (ÕÑ ËÏÂÏ). Ó ïàöèåíòîâ âòîðîé ãðóïïû íàáëþäàëàñü ãèïîàëüôàõîëåñòåðèíåìèÿ, ãèïåðòðèãëèöåðèäåìèÿ, ïîâûøåíèå óðîâíÿ ÕÑ ËÏÍÏ. Ïàöèåíòû òðåòüåé ãðóïïû èìåëè ïîâûøåíèå óðîâíÿ ÕÑ ËÏÎÍÏ, à òàêæå ãèïåðïðîäóêöèþ Àðî (òàáëèöà). Êðîìå òîãî, ó ïàöèåíòîâ âòîðîé è òðåòüåé ãðóïï áûëî óñòàíîâëåíî ïîâûøåíèå ÷àñòîòû âñòðå÷àåìîñòè àëëåëÿ Å4 ãåíà ÀðîÅ è àëëåëÿ D ãåíà ÀÑÅ. Òàêèì îáðàçîì, ó âñåõ îáñëåäóåìûõ ïàöèåíòîâ áûëè âûÿâëåíû ðàçëè÷íûå âàðèàíòû àòåðîãåííûõ äèñëèïèäåìèé, â îñíîâíîì õàðàêòåðèçóþùèõñÿ ïîâûøåíèåì óðîâíÿ òðèãëèöåðèäîâ è ñíèæåíèåì óðîâíÿ ÕÑ ËÏÂÏ, ÷òî ìîæåò ÿâèòüñÿ ïðè÷èíîé àòåðîñêëåðîòè÷åñêèõ èçìåíåíèé â ñîñóäàõ íèæíèõ êîíå÷íîñòåé è òðåáóåò íàçíà÷åíèÿ ãèïîëèïèäåìè÷åñêèõ ïðåïàðàòîâ (ðèñóíîê, à, á). 75 Ñðåäíèå çíà÷åíèÿ ïîêàçàòåëåé ëèïèäíîãî îáìåíà ó ïàöèåíòîâ ñ ãíîéíî-íåêðîòè÷åñêèìè ïîðàæåíèÿìè ïðè ñèíäðîìå äèàáåòè÷åñêîé ñòîïû ؼÉÌÈȹ Q ؼÉÌÈȹ Q ؼÉÌÈȹ Q ®ÇľÊ˾ÉÁÆ ÇºÒÁ ÅÅÇÄÕÄ «ÉÁ¼ÄÁϾÉÁ½Ô ÅÅÇÄÕÄ ¤¨¨ ¤¨¦¨ ¤¨§¦¨ Ï ð è ì å ÷ à í è å. ËÏÂÏ, ËÏÍÏ, ËÏÎÍÏ ëèïîïðîòåèíû âûñîêîé, íèçêîé è î÷åíü íèçêîé ïëîòíîñòè ñîîòâåòñòâåííî. a I D á Q Q Q Q Q Ðàñïðåäåëåíèå ÷àñòîò àëëåëåé I/D ïîëèìîðôèçìà ãåíà ÀÑÅ (à) è àëëåëåé ïîëèìîðôèçìà ãåíà Àðî Å (á) ó áîëüíûõ ñ ãíîéíî-íåêðîòè÷åñêèìè îñëîæíåíèÿìè ñèíäðîìà äèàáåòè÷åñêîé ñòîïû 76 Ïî ðåçóëüòàòàì èññëåäîâàíèÿ ìîæíî çàêëþ÷èòü ñëåäóþùåå. Ó âñåõ ïàöèåíòîâ ñ ãíîéíî-íåêðîòè÷åñêèìè ïîðàæåíèÿìè ïðè ÑÄÑ îòìå÷àþòñÿ ðàçëè÷íûå âàðèàíòû àòåðîãåííûõ äèñëèïèäåìèé. Ïðè ýòîì ïàöèåíòû âòîðîé è òðåòüåé ãðóïï ñî IIV ñòåïåíüþ ïîðàæåíèé íèæíèõ êîíå÷íîñòåé èìåþò ìàêñèìàëüíî âûðàæåííûé àòåðîãåííûé ñäâèã ïðîôèëÿ ëèïèäíîãî ñïåêòðà êðîâè. Ó ïàöèåíòîâ ïåðâîé ãðóïïû ñ I ñòåïåíüþ ïîðàæåíèé íèæíèõ êîíå÷íîñòåé íà ôîíå àòðîãåííîãî ñäâèãà ñîîòíîøåíèÿ àïîïðîòåèíîâ íàáëþäàþòñÿ íîðìàëüíûå óðîâíè ÕÑ ËÏÂÏ. Àíàëèç ðàñïðåäåëåíèÿ ãåíîòèïîâ è àëëåëåé èññëåäîâàííûõ ìîëåêóëÿðíî-ãåíåòè÷åñêèõ ìàðêåðîâ ïîçâîëèë âûÿâèòü, ÷òî àëëåëè Å4 ãåíà Àðî Å è D-àëëåëÿ ãåíà ACE äîñòîâåðíî ÷àùå âñòðå÷àþòñÿ ó ïàöèåíòîâ âòîðîé è òðåòüåé ãðóïï ñ ìàêñèìàëüíî âûðàæåííûì ïîðàæåíèåì íèæíèõ êîíå÷íîñòåé Òàêèì îáðàçîì, ñëåäóåò îòìåòèòü, ÷òî ñ ïîçèöèé ïðàêòèêè äëÿ õàðàêòåðèñòèêè ãíîéíî-íåêðîòè÷åñêèõ ïðîöåññîâ â íèæíèõ êîíå÷íîñòÿõ ó áîëüíûõ ñ ÑÄÑ íàèáîëåå ïðèåìëåìà êëàññèôèêàöèÿ Âàãíåðà. Îäíàêî îñíîâûâàÿñü òîëüêî íà íåé, ìû íå ìîæåì âûðàáîòàòü îïòèìàëüíóþ õèðóðãè÷åñêóþ òàêòèêó è àëãîðèòì êîìïëåêñíîãî ëå÷åíèÿ äëÿ êàæäîé êàòåãîðèè ïàöèåíòîâ. Ïîýòîìó, ïî íàøåìó ìíåíèþ, íåîáõîäèìî ó÷èòûâàòü âëèÿíèå ìåòàáîëè÷åñêèõ è ìîëåêóëÿðíî-ãåíåòè÷åñêèõ ôàêòîðîâ íà òå÷åíèå îñëîæíåííûõ ôîðì ñèíäðîìà äèàáåòè÷åñêîé ñòîïû è ñâîåâðåìåííî ïðîãíîçèðîâàòü âîçìîæíûå âàðèàíòû òå÷åíèÿ ãíîéíî-íåêðîòè÷åñêèõ îñëîæíåíèé ÑÄÑ è ðàçâèòèå ñåðäå÷íî-ñîñóäèñòûõ îñëîæíåíèé. Summary Petrova V.V., Kulikov Yu.F., Larionova V.I., Spesivtsev Yu.A. Role of medical and genetical factors in objective estimation of destructive complications of diabetic foot syndrome. Diabetic Foot Syndrome (DFS) a complex pathology that differs in mechanisms of forming. at least once in a lifetime it affects one of five patients, suffering from diabetes mellitus. Suppurative complications of diabetes are the leading reasons of amputations in developed countries. According to variety of etiology and pathogenesis, anatomical localizations, tissue damage depth and attended circumstances like presence of infection a classification, including most important factors should be created. This division is going to help to predict further course of DFS with decent probability. In our article we offer taking into consideration metabolism and molecular genetics aspects of pathogenesis within classification to work out optimal surgery tactics for every group of patients. Keywords : diabetes mellitus, diabetic foot syndrome, suppurative & necrotic destruction, dyslipihaemia, aterogenical blood profile, atherosclerosis, genes, alleles. Ëèòåðàòóðà 1. Pecoraro R.E. Diabetic skin ulcer classification for clinical investigations // Clin. Mater. 1991.Vol. 8. Ð. 257262. 2. Reiber G.E. Diabetic foot care: Financial implication and practice guidelines // Diabetes 1992. Vol. 37. Ð. 15951607. 3. Palumbo P.J, Melton L.J. Peripheral vascular disease and diabetes // Diabetes in America / Eds M.I. Harris, R.F. Hamman. Washington, 1995. NIH Publ. 85 1468, 121. 4. Pecoraro R.E, Reiber G.E. Classification of wounds in diabetic amputees // WOUNDS. 1990. Vol. 2. Ð. 6973. 5. Meggit B. Surgical management of the diabetic foot // Brit. J. Hosp. Med 1976. P. 22732. 6. Wagner F.W. The dysvascular foot: A system for diagnosis and treatment // Foot. Ankle. 1981. Vol. 2. Ð. 64122. 7. Jeffcoate W.J., Macfarlane R.M., Flether E.M. 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Treatment-based classification system for assessment and care of diabetic feet // J. Am. Pod. Med. Assoc. 1996. Vol. 86. P. 311316. 14. Lavery L.A., Harkless L.B., Johnson K. et al. Bacterial pathogens in infected puncture wounds in adults with diabetes // J. Foot. Ankle. Surg. 1994. Vol. 33. P. 9194. 15. Armstong D.G., Lavery L.A., Harkless L. Validation of a diabetic wound classification system // Diabet. Care. 1998. Vol. 5. P. 855859. 16. Calhoun J.H., Eng M., Cantrell J. et al. Treatment of diabetic foot infections: Wagner Classification, therapy, and outcome // Foot. Ankle. 1998. Vol. 9. P. 101106. 17. Apelqvist J., Agardh. The association between clinical factors and outcome of diabetic foot ulcers // Diabet. Res. Clin. Pract. 1992. Vol. 8. P. 43. 18. Van Acker K., De Block C. et al. The Choice of Diabetic Foot Ulcer Classification in Relation to the Final Outcome // WOUNDS. 2002. Vol. 14 (1). P. 1625. 19. Piaggesi A., Palumbo F. et al. Measurements in the Diabetic Foot // WOUNDS. 2005. Vol. 14(1). P. 1625. 20. Óäîâè÷åíêî Î.Â., Ãàëñòÿí Ã.Ð., Ñòàðîâåðîâà Ä.Í. è äð. Ðàñïðîñòðàítííîñòü ïîðàæåíèÿ íèæíèõ êîíå÷íîñòåé ó áîëüíûõ ñàõàðíûì äèàáåòîì â Ðåñïóáëèêå Òàòàðñòàí // Ñàõàð. äèàáåò. 2003. ¹ 3. C. 68. 21. Levin M.E. Preventing amputation in the patient with diabetes // Diabet. Care. 1995. Vol. 18(10). P. 13831394. 22. American Diabetes Association. Direct and Indirect Costs of Diabetes in the United States in 1992. Alexandria, Va: American Diabetes Association. 1993. 23. Reiberg G.E., Boyko E.J., Smith D.G. Lower extremity foot ulcers and amputations in diabetes // National Diabetes Data Group / Ed. Diabetes in America. Washington, 1995. P. 409428. 24. The Diabetic Foot. Proceedings of the First International Simposium on the Diabetic Foot. The Netherlands, 1991. Còàòüÿ ïîñòóïèëà â ðåäàêöèþ 13 èþëÿ 2006 ã.
