Zusammenfassung
Für das Studium der Gallesekretion an gallenkanülierten Schweinen wurde eine Apparatur entwickelt, welche die ausgeschiedene Galle entsprechend der Sekretionsrate wieder zurückführt. Gleichzeitig erlaubt diese Apparatur die Messung des Gallevolumens und die Ziehung repräsentativer Galleproben für die Bestimmung der Substratkonzentrationen.
An Schweinen mit einer mittleren Lebendmasse von 45 ± 3 kg, welche zweimal täglich eine normale Futterration erhielten, wurde nach einer achttägigen postoperativen Erholungsphase eine mittlere Galleflußrate von 2181 ± 133 ml/Tag gemessen. Die täglichen Sekretionsraten der Gallensäuren, Phospholipide und Cholesterin wurden zu 31,8 ± 9,2 mmol, 7,6 ± 1,3 mmol und 1,5 ±0,4 mmol bestimmt.
1 We administered the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin at a daily dose of 1 mg kg 71 body weight to cholesterol-fed (0.03%) heterozygous Watanabe heritable hyperlipidaemic rabbits, an animal model for heterozygous familial hypercholesterolaemia. 2 After 12 months of cholesterol treatment, immunohistochemistry with the monoclonal antibody 9D9 was used to detect hepatic low density lipoprotein (LDL) receptors, which were quanti®ed by densitometry. In addition we determined LDL receptor mRNA by competitive reverse transcriptase polymerase chain reaction. The cholesterol precursor lathosterol and the plant sterol campesterol were analysed by gas-liquid chromatography. 3 The drug reduced total plasma cholesterol levels by 51% (P=0.04), when compared to the control group. Unexpectedly, hepatic LDL receptor density and mRNA showed no signi®cant dierences between the groups. Total plasma levels of lathosterol and campesterol also revealed no signi®cant dierences between the groups, if expressed relative to plasma cholesterol. 4 The ®ndings suggest that mechanisms other than induced hepatic LDL receptors are responsible for the cholesterol-lowering eect of pravastatin in this animal model. We propose a reduced cholesterol absorption eciency compatible with similar campesterol levels between both groups observed in our study.
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