Effect of zhenqing recipe on non-alcoholic fatty liver in type 2 diabetes rats and the expression of SIK1 / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Zhenqing Recipe (ZQR) on non-alcoholic fatty liver (NAFL), and the expression of hepatic salt-inducible kinase 1 (SIK1) and sterol-regulatory element binding protein-ic (SREBP-lc) in type 2 diabetes rats.</p><p><b>METHODS</b>A rat model of type 2 diabetes was established by high fat/sucrose diet combined with intraperitoneal injection of small dose streptozotocin (STZ) . Modeled rats were randomly divided into the model group, the ZQR group, and the metformin group, 8 in each group. Eight rats were recruited as a normal control group. ZQR at the daily dose of 12 g crude drugs/kg was administered to rats in the ZQR group by gastrogavage. Metformin suspension at the daily dose of 150 mg/kg was administered to rats in the metformin group by gastrogavage. Equal volume of distilled water was administered to rats in the normal control group and the model group. All medication lasted for 12 weeks. The levels of fasting blood glucose (FBG), free fatty acid (FFA), serum triglyceride (TG), serum total cholesterol (TC), serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected. The body weight and wet liver weight were weighed, and the liver weight index calculated. The liver TG content was measured. The pathological changes of liver and the expression of SIK1 were observed by HE staining and immunohistochemistry. The mRNA and protein expression of SIK1 and SREBP-1c were detected using RT-PCR and Western blot.</p><p><b>RESULTS</b>Compared with the normal control group, FBG, FFA, TG, TC, ALT, AST, liver weight index, and liver TG contents significantly increased (P < 0.01); liver steatosis was severe, the mRNA and protein expression of SIK1 obviously decreased (P < 0.01); mRNA and protein expression of SREBP-1c increased (P < 0.01). After drug therapy, compared with the model group, FBG, FFA, TG, TC, ALT, AST, and liver weight index significantly decreased, liver TG contents significantly decreased, the mRNA and protein expression of SIK1 obviously increased, while mRNA and protein expression of SREBP-1c obviously decreased (P < 0.05, P < 0.01) in the ZQR group and the metformin group (P < 0.05, P < 0.01); and the pathological changes were also improved. All the indices were improved more in the ZQR group (all P < 0.05).</p><p><b>CONCLUSION</b>In this experiment, we found that the expression of SIK1 decreased in NAFL rats with type 2 diabetes. ZQR could alleviate lesion of NAFL type 2 diabetes rats possibly by up-regulating hepatic SIK1 expression at mRNA and protein levels.</p>

Jueming Prescription reduces body weight by increasing the mRNA expressions of beta3-adrenergic receptor and uncoupling protein-2 in adipose tissue of diet-induced obese rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the antiobesity effect of Jueming Prescription (JMP), a Chinese herbal medicine formula, and its influence on mRNA expressions of beta3 adrenergic receptor (beta3-AR) and uncoupling protein-2 (UCP-2) in adipose tissue of diet-induced obese rats.</p><p><b>METHODS</b>Fifty male Sprague-Dawley rats were randomly divided into the normal control group (n =8) that was on a standard chow diet, and the obese model group (n =42) that was on a diet of high fat chow. Two weeks after the high fat diet, 29 obese rats in the obese model group were further randomly divided into 3 groups: the untreated obese model group (n =9), the metformin group (n =10, metformin 300 mg kg⁻¹ day)⁻¹, and the JMP group (n =10, JMP 4 g kg⁻¹ day⁻¹). After 8-week treatment, body weight, wet weight of visceral fat, and percentage of body fat (PBF) were measured. The levels of fasting blood glucose, serum lipids, and insulin were assessed, and insulin sensitivity index (ISI) was calculated. The adipose tissue section was stained with hematoxylin-Eosin, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expressions of beta3-AR and UCP-2 from the peri-renal fat tissue were determined by real-time reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Compared with the obese model group, treatment with JMP resulted in significantly lower body weight, wet weight of visceral fat, PBF, and diameter of adipocytes, and significantly higher level of high-density lipoprotein cholesterol, ISI (all P<0.01), JMP increased the mRNA expressions of beta3-AR and UCP-2 from perirenal fat tissue (P <0.05, P<0.01).</p><p><b>CONCLUSIONS</b>JMP could reduce body weight and adipocyte size; and the effect was associated with the up-regulation of beta3-AR and UCP-2 expressions in the adipose tissue and improvement of insulin sensitivity.</p>

Effects of zhenqing recipe and earthworm on the expressions of transforming growth factor-beta1 and plasminogen activator inhibitor 1 in renal tissues of type 2 diabetic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effects of Zhenqing Recipe (ZQR) and earthworm on the expressions of transforming growth factor-beta1 (TGF-beta1) and plasminogen activator inhibitor-1 (PAI-1) in renal tissues of type 2 diabetes mellitus (T2DM) rats.</p><p><b>METHODS</b>The T2DM model rats induced by high sucrose/fat feeding and low dose streptozotocin injecting were randomly divided into the model group, the ZQR group, and the earthworm group. A normal control group was also set up. ZQR extract was given at the daily dose of 24 g/kg body weight by gastrogavage to rats in the ZQR group. The earthworm extract was given at the daily dose of 2.6 g/kg body weight by gastrogavage to rats in the earthworm group. Equal volume of distilled water was given to rats in the normal control group and the model group by gastrogavage. The medication was once daily for 8 successive weeks. The fasting blood glucose (FBG), serum PAI-1, 24-h urinary albumin excretion (UAE), and endogenous creatinine clearance rate (CCr) were detected. The structural changes of renal tissues stained with Periodic Acid-Schiff were observed by light microscope. The expressions of TGF-beta1 and PAI-1 were analyzed by immunohistochemistry. And the mRNA and protein expressions of TGF-beta1 and PAI-1 in the renal cortex were detected by Real-time PCR and Western blot respectively.</p><p><b>RESULTS</b>Compared with the normal control group, the FBG, serum PAI-1, UAE, the mRNA and protein expressions of TGF-beta1, and PAI-1 significantly increased in the model group, and CCr obviously decreased (P<0.01). Compared with the model group, FBG, serum PAI-1, UAE obviously decreased (P<0.01) and CCr obviously increased (P<0.05) in the ZQR group. FBG was not obviously lowered in the earthworm group. The serum PAI-1 and UAE both decreased obviously (P<0.05, P<0.01) and CCr increased (P<0.05) in the earthworm group. The effects of ZQR were superior to the earthworm. The renal pathological changes got improved in the ZQR group and the earthworm group. The mRNA and protein expressions of TGF-beta1 and PAI-1 significantly decreased in the ZQR group and the earthworm group, especially in the ZQR group.</p><p><b>CONCLUSIONS</b>Early application of ZQR and earthworm in treatment of T2DM rats with nephropathy was effective in protecting the kidney. Its mechanism may possibly be correlated with inhibition of TGF-beta1 expression, resulting in down-regulation of PAI-1 expression. ZQR showed better effects than earthworm.</p>

Modulative effect of zhenqing recipe on expressions of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in experimental type 2 diabetic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Zhenqing Recipe (ZQR) on renal structure and expressions of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in experimental type 2 diabetic rats.</p><p><b>METHODS</b>The rat models of type 2 diabetic were set up by intraperitoneally giving small-dose streptozotocin (STZ) after fed with high carbohydrate and high fat diets for one month. The model rats were randomly divided into the model group,the high and low dose ZQR-treated groups,and the enalapril-treated group; a normal control group was also established. The course of treatment continued 8 weeks. The expressions of MMP-9, TIMP-1, and fibronectin (FN) in renal tissues were detected by immunohistochemistry. The morphological changes of glomeruli and renal tubules were checked by microscopy.</p><p><b>RESULTS</b>Compared with the normal control group, the expression of TIMP-1 and FN increased and MMP-9 decreased in the model group; the treated groups could decrease the expressions of TIMP-1 and FN, and increase the expression of MMP-9, especially the high-dose ZQR group had the best effect. The morphological changes of renal tubules and glomerulus in the treated groups were improved better as compared with the model group.</p><p><b>CONCLUSION</b>The protective effect of ZQR on renal structure may be achieved by modulating the expressions of MMP-1 and TIMP-1.</p>