Ursolic acid alleviates the injury of human aortic endothelial cells induced by high glucose and high fat / 中国临床药理学与治疗学

AIM: To investigate the effect and mechanism of ursolic acid on high glucose and high-fat injury of human aortic endothelial cells. METHODS: MTT method was used to select the appropriate injury concentration of high glucose and sodium palmitate and UA pre incubation concentration. The levels of NO and ROS, the release rate of lactate dehydrogenase and the activities of antioxidant enzymes including total superoxide dismutase, catalase and glutathione peroxidase were detected by kit. The expression of endothelial nitric oxide synthase, intercellular adhesion molecule, vascular cell adhesion molecule caspase-1 and GSDMD were detected by Western blot. The protective effect of UA on HAEC was observed. Hoechst33342 combined with PI fluorescence staining was used to detect the whole state of cell membrane to explore the occurrence of pyroptosis. RESULTS: Pre-incubation with UA (1 and 5 μmol/L) could reduce the damage of HAEC caused by high glucose and high fat (30 mmol/L Glu + 0.1 mmol/L SPA), enhance HAEC activity, increase NO release and eNOS protein expression, alleviate oxidative stress injury, reduce the protein expression of adhesion molecules and reduce the occurrence of pyroptosis. CONCLUSION: UA may reduce the damage of endothelial cells by inhibiting the oxidative stress response and the occurrence of pyroptosis induced by high glucose and high fat.

Effects of Wuling Powder on Insulin Resistance of Mice Induced by High Lipid Diet / 中国中医药信息杂志

Objective To investigate the effects of Wuling Powder on insulin resistance of C57BL/6J mice induced by high lipid diet, and discuss the mechanism. Methods C57BL/6J mice were randomly divided into six groups:normal group, model group, rosiglitazone group, Wuling Powder in low, middle, and high dose groups, 10 mice per group. Besides the normal group, other five groups were fed with high fat and sugar diet, with a purpose to establish insulin resistance model. Normal group and model group were given pure water. Rosiglitazone group received a gavage with rosiglitazone of 0.75 mg/kg. Wuling Power low, middle, and high groups received gavage with Wuling Power of 1.23, 3.69, 11.07 g/kg, respectively, the does volume was 0.2 mL/10 g, once a day. The weight and abdominal girth were detected every week. At the end of the sixth week, mice were given 12-hour fasting, and their eyeball were taken for blood. The body weight, length, and fat in abdomen and both kidneys were detected. Paraffin section was made with HE staining. FPG and FINS of each group were detected. ISI and IRI were calculated, and TC and TG were detected. Results Compared with the model group, Wuling Powder can significantly reduce the body weight and abdominal girth of mice (P<0.01, P<0.001), improve liver fatty degeneration, lower the FPG, FINS, TCH, TG, IRI, and increase the ISI in mice (P<0.05, P<0.01). Conclusions Wuling Powder has the effect of preventing insulin resistance of C57BL/6J mice induced by high lipid diet.

High lipid-mediated endoplasmic reticulum stress in human glomerular mesangial cell injury under inflammation condition: The role and mechanisms / 第二军医大学学报

Objective To study the role of high lipid-mediated endoplasmic reticulum stress in human glomerular mesangial cells (HMCs) injury under inflammation condition, and to explore the mechanism of lipid-induced kidney injury. Methods HMCs were divided into control group, high lipid group, inflammatory stress group, high lipid plus inflammatory stress group, and high lipid plus inflammatory stress plus 4-phenylbutyric acid (4-PBA) group. After culture for 24 h, 48 h, and 72 h, Oil red O staining was used to evaluate lipid droplet accumulation in the cells; cell proliferation was assessed by MTT assay; expression of GRP78 protein was measured by immunocytochemistry method; and the levels of Gi?P78 and FN mRNA were examined by real-time PCR. Results (1) Compared with control group, the high lipid group, inflammatory stress group and high lipid plus inflammatory stress group had significantly increased intracellular cholesterol levels (all P < 0. 01), significantly higher FN mRNA levels (all P<0. 01), and significantly faster cell proliferation (all P<0. 01), which was in a time-dependent manner. Compared with high lipid plus inflammatory stress group, 4-PBA group had significantly reduced lipid deposition (all P<0. 01), slower cell proliferation (all P<0. 01) and lower FN mRNA expression (P<0. 05, P<0. 01) induced by high lipid. (2) Compared with control group, high lipid group, inflammatory group and high lipid plus inflammatory stress group had significantly increased expression of GRP78 mRNA and protein (P<0. 05,P<0. 01), and the expression in 4-PBA treatment group was significantly lower than that in the high lipid plus inflammatory stress group (all P<0. 01). (3) After treatment with high lipid or inflammation for 24 h, 48 h and 72 h, the intracellular cholesterol level was positively correlated with mesangial cell proliferation and expression of GRP78 protein and FN mRNA (all P < 0. 01). The cellular expression of GRP78 protein was positively correlated with mesangial cell proliferation and FN mRNA expression (all P< 0. 05). Conclusion High lipid can induce glomerular mesangial cell injury through activating endoplasmic reticulum stress in HMCs under inflammation stress condition.

Breeding of high lipid producing strain of Geotrichum robustum by ion beam implantation

To obtain an industrial strain with high lipid yield, the wild strain G0 of Geotrichum robustum was mutated by means of nitrogen ions implantation. Mutagenic effects of strain G0 by low energy N+ ion implantation were studied. The experimental results indicated that the survival rate curve took a "saddle" shape, and the positive mutation rate was increased to 22.00 percent at the dose of nitrogen ions 2.0 x 10(15) ions/cm² when the survival rate was 28.60 percent. By repeated screening, a high lipid producing strain G9 was obtained. The biomass, lipid content and lipid yield of the mutant can reach 40.25 g/L, 71.14 percent and 28.63 g/L after cultured in a 5L fermenter for 8 days, increasing by 52.81 percent, 68.82 percent and 157.93 percent to those of wild strain, respectively. Analysis results on fatty acids composition and relative content by gas chromatography and mass spectrometry showed that the lipid in strain G9 was mainly composed of 16-carbon and 18-carbon fatty acids, including 37.360 percent oleic acid, 23.631 percent palmitic acid, 4.458 percent linoleic acid and 26.465 percent stearic acid. Such compositional features were quite similar to plant oil. Geotrichum robustum strain G9 may be an ideal high lipid producing strain for biodiesel production.

Effects of Atorvastatin on the Induction of Experimental Cerebral Aneurysm in a High Lipid Diet Rat Model / 대한뇌혈관외과학회지

OBJECTIVE: Previously, we reported that a high lipid diet significantly increases the induction rate of cerebral aneurysm (CA) formation in an experimentally induced CA rat model, suggesting that hypercholesterolemia with chronic inflammation leads to aneurysm formation. To elucidate the role of hypercholesterolemia in CA formation, experimentally induced CA was evaluated in rats fed a high lipid diet and treated with low and high doses of atorvastatin. METHODS: Thirty-seven, 7-week-old male Sprague-Dawley rats underwent a CA induction procedure. The control animals (n = 11) were fed a normal diet, and the experimental animals (n = 26) were fed a diet containing high lipid content for 3 months. The experimental group comprised a high-dose atorvastatin group (20 mg/kg/day, n = 15) and low-dose atorvastatin group (1 mg/kg/day, n = 11). Three months after the operation, induction of CA formation in the three groups was analyzed. RESULTS: Induced CA formation was 67%, 63%, and 36% in the control, high lipid/high atovastatin, and high lipid/low atovastatin group, respectively. The differences resulting from high-dose and low-dose atorvastatin were significant (Pearson k2, P = 0.028 and 0.029, respectively). CONCLUSIONS: A high lipid diet can significantly increase induction of CA formation. However, the lack of decreased induction in atorvastatin-treated animals suggests that high and low doses of atorvastatin do not inhibit the potential effects of hypercholesterolemia on CA formation. Further studies, such as those utilizing apolipoprotein E knockout mice, are necessary to elucidate the exact role of hypercholesterolemia in the pathophysiology of CA.

Difference in Induction Rate of Experimental Cerebral Aneurysm According to High Salt, High Lipid and Normal Diet / 대한뇌혈관외과학회지

OBJECTIVE: An intracranial aneurysm is an important acquired cerebrovascular disease that can cause a catastrophic subarachnoid hemorrhage. Atherosclerosis is one of possible mechanism, but its contribution to aneurysm formation is unclear. Experimentally induced cerebral aneurysm rate by high lipid diet was evaluated and compared with high salt and normal diet to elucidate the role of lipid metabolism in the process of cerebral aneurysm formation. METHODS: Thirty-seven 7-week-old male Sprague-Dawley (SD) rats received a cerebral aneurysm induction procedure. The control animals (n=11) were fed a normal diet, and the experimental animals were fed a diet containing 8% salt (n=15) and high lipid (n=11) for three months. Three months after the operation, the rats were killed, their cerebral arteries were dissected, and the regions of the bifurcation of the right anterior cerebral artery-olfactory artery (ACA-OA) bifurcations were examined histologically and aneurysm induction rates among three groups were analysed. RESULTS: Average systolic blood pressures after 3 months feeding in three groups (high salt diet group, high lipid diet group and normal diet group) were 175.9+/-3.4 mmHg, 133.7+/-5.1 mmHg and 128+/-2.9 mmHg, respectively. The difference between high lipid group and normal diet group was not significant (P=0.215). The aneurysm induction rate in three group were 87%, 63% and 36%. The difference between high lipid diet group and normal diet group was significant (Pearson k2, P=0.029). CONCLUSIONS: High lipid diet significantly increase the cerebral aneurysm induction rate in experimentally induced cerebral aneurysm model of rats. That suggests a possible adverse role for hyperlipidemia leading to aneurysm formation. Further studies are necessary to elucidate the exact role of hyperlipidemia in the pathophysiology of cerebral aneurysm.

Changes of angiotensin1at different stages of atherosclerosis in rats / 第二军医大学学报

Objective:To investigate the relation between the angiotensinⅡ(AngⅡ)levels in thoracic aorta and plasma and atherosclerosis(AS).Methods:Totally40healthy male Wistar rats were randomly divided into4groups(n=10).Four different feeding methods,including normal diet,high lipid,high lipid+vitamin D overload,and high lipid+vitamin D over-load+endothelium injury,were used for inducing AS in rats.The thickness of intima was taken as the index of AS severity, radio-immunity analysis was used to assay AngⅡin each group in thoracic aorta and plasma.Results:Only rats in high lipid diet group did not develop AS plaque;high lipid+vitamin D only resulted in AS fibrous plaque with VSMC proliferation;high lipid+vitamin D+endothelium injury formed ripe AS plaque.The thickness of intima and AngⅡof thoracic aorta in-creased gradually compared with control group(P