1.Study on the Percutaneous Permeability of Hydrocortisone Cream with Different Substrates in Diabetic Model Rats
Jianming ZHANG ; Shasha LI ; Zhuoji XIE ; Dongling GUAN ; Guofeng LI
China Pharmacy 2015;(19):2667-2669,2670
OBJECTIVE:To study the percutaneous permeability of Hydrocortisone cream with different substrates in diabetic model rats. METHODS:The Hydrocortisone O/W(oil/water)cream,water-soluble cream and oil-soluble cream were respectively prepared. Wistar rats were randomly divided into normal control group and model group. Model group was given streptozotocin(40 mg/kg)to reproduce diabetic model. Franz diffusion cell percutaneous test and HPLC were used to detect the percutaneous permea-bility rates of Hydrocortisone O/W cream,water-soluble cream and oil-soluble cream in rats of 2 groups. RESULTS:Compared with normal control group,the percutaneous permeability rates of Hydrocortisone O/W cream and water-soluble cream were obvi-ously increased,with significant difference(P<0.05);there was no significant difference in the percutaneous permeability rate of oil-soluble cream (P>0.05). CONCLUSIONS:Hydrocortisone O/W cream and water-soluble cream are easier to go through the skin of diabetic model rats,and Hydrocortisone oil-soluble cream is hard.
2.Pharmacological Effect of Nuanxinkang Powder on Ventricular Remodeling in Post-infarction Mice Through"Metabolic-Inflammatory"Network Regulating Macrophage Polarization
Zhijun LIN ; Zixin CHEN ; Jialin JIANG ; Xin DONG ; Zhuoji GUAN ; Lingjun WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(2):159-167
Objective To explore the mechanism of Nuanxinkang Powder(aka.NXK,composed of Ginseng Radix et Rhizoma Rubra and Ilex Pubescens Radix)on improving ventricular remodeling in post-infarction mice based on the"metabolic-inflammatory"network regulating macrophage polarization.Methods ①Thirty C57BL/6J male mice were randomly divided into three groups:sham-operation group,model group,and NXK group(1.65 g·kg-1),with 10 mice in each group;the mouse model of myocardial infarction was replicated using left anterior descending coronary artery ligation;and the drug was administered by gavage once a day for 4 consecutive weeks.Masson staining was used to detect collagen deposition in myocardial tissue;ultrasound was used to detect cardiac function in mice:left ventricular ejection fraction(LVEF),left ventricular anterior wall thickness at end-systole(LVAWS)and left ventricular anterior wall thickness at end-diastole(LVAWD);flow cytometry was used to detect distribution of cardiac macrophages in mice;qPCR was used to detect mRNA expressions of lactate dehydrogenase A(LDHA),carnitine palmitoyltransferase 1(CPT-1),glucose transport protein 4(GLUT4),isocitrate dehydrogenase(IDH),and succinate dehydrogenase(SDHa)in heart tissue.②NXK was given 1.15 g·kg-1 NXK suspension to rats by gavage twice a day for 5 consecutive days to prepare NXK-containing serum.Lipopolysaccharide(LPS)-induced RAW 264.7 cells were used to construct a pro-inflammatory macrophage model.The cells were grouped into the following groups:blank serum control group(medium containing 5%blank serum+5%fetal bovine serum),NXK drug-containing serum group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum),lipopolysaccharide group(medium containing 5%blank serum+5%fetal bovine serum+200 μg·mL-1 lipopolysaccharide),NXK drug-containing serum+ lipopolysaccharide group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum+200 μ g·mL-1 lipopolysaccharide),all the groups were intervened for 16 hours.Glycolysis stress test was used to detect the level of glycolysis in RAW 264.7 cells;qPCR was used to detect the mRNA expression of mitochondrial pyruvate carrier(MPC1)in RAW 264.7 cells;and MitoSox Red fluorescent staining was used to detect the level of oxidative stress damage in mitochondria of RAW 264.7 cells.Results ①Compared with the sham-operation group,the blue-stained area of cardiac collagen fibres in mice of the model group was significantly increased,accompanied by thinning of the ventricular wall and enlargement of the left ventricular cavity;cardiac function indexes,such as LVEF,LVAWS,LVAWD,etc.,were all significantly reduced(P<0.01,P<0.001);the mRNA expressions of LDHA and CPT-1 were significantly up-regulated in the cardiac tissues of mice(P<0.05),and the mRNA expressions of GLUT4,IDH and SDHa were significantly down-regulated(P<0.05,P<0.01),and CD86 staining positive cell was significantly increased(P<0.001).Compared with the model group,mice in the NXK group showed a significant decrease in cardiac collagen fiber deposition and an increase in the thickness of the ventricular wall;cardiac function indexes such as LVEF,LVAWS and LVAWD were significantly increased(P<0.05,P<0.01,P<0.001);and the mRNA expressions of LDHA and CPT-1 in the cardiac tissues of the mice were significantly down-regulated(P<0.01,P<0.001),mRNA expressions of GLUT4,SDHa and IDH were significantly up-regulated(P<0.01),and the number of CD86 positive cells was significantly reduced(P<0.001).②Compared with the blank serum control group,the cytosolic glycolysis level and ROS level of macrophages in the NXK serum-containing group did not change significantly(P>0.05),whereas the glycolysis level and ROS level of macrophages in the lipopolysaccharide group were significantly increased(P<0.01),and the mRNA expression of MPC1 was significantly down-regulated(P<0.001).Compared with the lipopolysaccharide group,the macrophage glycolysis level and ROS level were significantly reduced in the NXK serum-containing + lipopolysaccharide group(P<0.05,P<0.01),and mRNA expression of MPC1 was significantly up-regulated(P<0.001).Conclusion NXK can reduce myocardial fibrosis and ventricular remodeling after myocardial infarction and improve cardiac function in mice,and its mechanism may be related to the down-regulation of mRNA expression of LDHA in cardiac tissues,the up-regulation of mRNA expression of GLUT4,the improvement of cardiac glucose uptake after myocardial infarction,the inhibition of pro-inflammatory macrophage glycolysis,the increase in the expressions of SDHa and IDH to alleviate the accumulation of succinate and citrate,and the reduction of reactive oxygen species(ROS)generation,thereby reducing pro-inflammatory macrophage hyperpolarisation.