1.Notoginseng Radix et Rhizoma Powder Treats Dyslipidemia via PI3K/Akt Signaling Pathway
Xiaoyan DU ; Lanhua AN ; Jinsheng ZHANG ; Kangli XU ; Li TIAN ; Sanqiang LI ; Xixian ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):88-95
ObjectiveTo evaluate the clinical efficacy and safety of Notoginseng Radix et Rhizoma powder in treating dyslipidemia by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodSixty patients with dyslipidemia (syndrome of combined phlegm and stasis) treated in the Third Affiliated Hospital of Henan University of Chinese Medicine from May 2021 to June 2022 were selected in this study and randomized into two groups according to the randomized, double-blind control principle. The control group was treated with Xuezhikang capsules + Notoginseng Radix et Rhizoma powder placebo and the observation group with Notoginseng Radix et Rhizoma powder + Xuezhikang capsules placebo for 6 weeks. The clinical efficacy, traditional Chinese Medicine (TCM) syndrome scores, and liver and kidney function indicators were evaluated at weeks 0, 3, and 6. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the expression of vascular endothelial growth factor (VEGF), kinase insert domain receptor (KDR), epidermal growth factor (EGF), and epidermal growth factor receptor (EGFR) in the peripheral serum. Quantitative Real-time PCR was employed to measure the mRNA levels of KDR, EGFR, PI3K, and Akt in the mononuclear cells of the peripheral blood. ResultThe observation group (83.33%) showed the total effective rate comparable to that of the control group (89.66%) and no adverse reactions. Compared with before treatment, the patients in the observation group showed decreased TCM syndrome score and serum levels total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) and after being treated for 3 and 6 weeks (P<0.05), the level of high-density lipoprotein cholesterol (HDL-C) showed an upward trend, but the difference was not statistically significant. After treatment, the two groups showed no significant differences. Compared with that before treatment, the mRNA expression of PI3K, Akt and EGFR in peripheral blood mononuclear cell and the expression of EGF, VEGF and KDR in serum of the observation group showed a downward trend with time, in which the mRNA expression of PI3K, Akt, VEGF and KDR decreased more significantly (P<0.05),The expression levels of KDR mRNA and serum EGFR show a trend of first increasing and then decreasing.Compared with the control group after treatment, there was no statistically significant difference in mRNA expression of PI3K, Akt, EGFR, and KDR, as well as serum levels of EGF, EGFR, VEGF, and KDR between the two groups of patients at the same time point. ConclusionNotoginseng Radix et Rhizoma powder is safe and effective in correcting dyslipidemia. It may inhibit the PI3K/Akt signaling pathway by down-regulating the expression of VEGF/KDR to lower the blood lipid level.
2.Comparison of histological characteristics of two experimental mouse abdominal aortic aneurysm models
Weilai FU ; Kangli TIAN ; Congcong XIA ; Haole LIU ; Jiaying SUN ; Daxin CHENG ; Enqi LIU ; Yankui LI ; Sihai ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(3):383-389
【Objective】 To compare the histological characteristics of porcine pancreatic elastase (PPE) induced abdominal aortic aneurysms (AAA) and angiotensin Ⅱ (AngⅡ) induced AAA in mice. 【Methods】 In the PPE group, the mouse abdominal aorta segment from the infrarenal abdominal aorta to the iliac artery was isolated and its branch arteries were ligated to avoid leakage during PPE perfusion. We perfused the isolated aorta segment with a PPE solution at a concentration of 1.5 U/mL for 5 min and then closed the abdominal cavity. The diameter of the abdominal aorta was measured before and 14 days after the surgery, and the perfusion segment of the arteries was collected at day 14 after the surgery. The histological characteristics of the aneurysm were analyzed and graded by histological and immunohistochemical methods. In the AngⅡ group, ten apolipoprotein E knockout mice were prepared, and AngⅡ [1 000 ng/(kg·min)] was infused with osmotic pumps for 28 days. The aorta was separated and the aneurysm aorta segment was analyzed. The wild type mice were used as normal health controls. 【Results】 In the PPE group, the diameter of the PPE perfused aorta segments increased and was significantly larger than the basal diameter [(0.52±0.02) mm vs. (1.23±0.11) mm] at day 14 after surgery. All the ten mice developed AAA after PPE application. The histological results showed typical pathological features of AAA in PPE perfused mice, such as elastic fiber breakage, smooth muscle exhaustion, and increased inflammation. Six of the ten mice developed aneurysms after AngⅡ infusion (6/10). The aneurysms/dilatations were mostly in the suprarenal abdominal aorta, but also in the thoracic aorta and aortic arch. The histology analysis showed that the formation of arterial dissection was common after AngⅡ infusion, and the typical vascular “false lumen” was found. The breakage of elastic fibers, the exhaustion of smooth muscle damage, and the inflammatory response were not as typical as the PPE model in AngⅡ perfused animals. 【Conclusion】 The histological characteristics of PPE induced AAA are very typical and well present the inflammatory process in the development of aneurysm. The AngⅡ model is suitable for the study of aneurysms combined with aortic dissection. Both models have their own advantages and can complement each other.